Donald Trump’s accusation that Hillary Clinton is playing the “woman’s card” and would be a failed candidate if she were a man touched off a contentious debate about gender politics and sexism that seems likely to define the presidential election as much as any issue.

While celebrating sweeping victories in five Republican primaries Tuesday night, Trump mocked the qualifications of the Democratic front-runner, saying she would be a bad president who lacks “strength.” The remarks seemed a preview of a general-election strategy to use Clinton’s potential to be the first female president against her.

“Frankly, if Hillary Clinton were a man, I don’t think she’d get 5 percent of the vote. The only thing she’s got going is the woman’s card,” Trump said in a news conference at Trump Tower. “And the beautiful thing is, women don’t like her.”

That was a significant expansion of Trump’s by-now-familiar claims that Clinton is unqualified — and one that made New Jersey Gov. Chris Christie’s wife, standing behind Trump before the TV cameras, appear to grimace.

It also crystallized the question of how the nation will reckon with its first presidential election between a man and a woman. What was once subtext — latent sexism in American life and the question of what is and is not off-limits when contemplating a woman as commander in chief — is now a full part of the political conversation.

“What’s shaping up is a battle for the ages,” said David Brock, a Clinton confidant who heads the pro-Clinton super PAC Correct the Record.

“You’ve got one candidate who is vying to be the first woman president and is embracing the historic nature of her own candidacy, and on the other hand, you’ve got Trump, who represents a kind of retrograde social structure of the past” that is blatantly sexist, Brock said. “There’s no better foil for Hillary.”

Clinton allies and the campaign itself have been startled by what some call Trump’s unsubtle line of attack, which stands in dramatic contrast with the more subtle presence of race in President Obama’s historic election eight years ago.

But most Clinton allies consider the newly escalated gender wars of 2016 a helpful point of comparison that she can use to rally women’s support and show how each candidate might behave as president.

“They might make flashy headlines, but Trump’s comments aren’t a joke,” the campaign wrote Wednesday. “Hillary can handle these attacks. Millions of women shouldn’t have to.”

As if to validate the importance of female voters and Trump’s weakness with them, GOP rival Ted Cruz on Wednesday announced that he was choosing Carly Fiorina as his running mate. Both Cruz and Fiorina criticized Trump and his rhetoric.

In television interviews Wednesday, Trump dismissed critics who called the election-night remarks sexist.

“It’s not sexist. It’s true. It’s just a very, very true statement. If she were a man, she’d get 5 percent. She’s a bad candidate. She’s a flawed candidate,” Trump said Wednesday on ABC’s “Good Morning America.” “She’s not going to do very well in the election, and I look forward to showing that.”

He also made fun both of Clinton’s delivery on the stump and of the social niceties — or political taboo — that says you’re not supposed to make fun of that.

“I haven’t quite recovered — it’s early in the morning — from her shouting that message,” he said on MSNBC’s “Morning Joe.” “And I know a lot of people would say you can’t say that about a woman because, of course, a woman doesn’t shout, but the way she shouted that message was not,” and with that Trump broke off with a dismissive, “eww.”

“I guess I’ll have to get used to a lot of that over the next four or five months,” he added, while also saying that he expects to do well with female voters.

Some responses on Clinton’s behalf were outraged and some mocking. And some sought to raise money from what Clinton allies see as an unappealing glimpse into both Trump as a Republican standard-bearer and a slice of the GOP electorate that is receptive to language and viewpoints other politicians have been schooled to avoid.

“Women still face too many barriers — a president shouldn’t be part of the problem. Comments like Trump’s set us back,” Clinton said in one of a blizzard of Twitter messages about the remarks Wednesday.

The real estate mogul has won female voters on average by 10 percentage points over his rivals in primary contests this year. On Tuesday, he won by more than 20 points among female voters in Connecticut, Maryland and Pennsylvania.

But Trump’s successes in winning Republican women has not translated to popularity with women or men in the broader electorate, where he continues to be deeply unpopular.

A USA Today/Suffolk University poll released this week found 66 percent of likely women voters nationwide have an unfavorable view of Trump, compared with 48 percent who have a negative opinion of Clinton. Among men the two are closer — 57 percent see Trump negatively while 61 percent say the same of Clinton.

“He continues to paint women with a broad, reductive brush, which may be a great strategy in appealing to his very particular audience of primary voters who have found his offensive tone endearing,” said Stephanie Schriock, who heads Emily’s List, a group that promotes and funds Democratic women running for office. “But in a general election, it is really difficult to shift from the place where he is to being presidential.”

Women are far more likely to have intensely negative views of Trump. A Washington Post-ABC News poll this month found 64 percent of women feeling “strongly unfavorable” toward Trump, compared with 41 percent of men.

Trump has consistently trailed Clinton, as well as Democratic candidate Bernie Sanders, in general-election matchups. The USA Today/Suffolk University poll found Clinton leading Trump by 11 percentage points, fueled by a 21-point lead among women. Women have historically leaned more toward Democrats than men have, but Trump’s deep unpopularity with women threatens to diminish his Republican support.

Despite the potential for a gender gap in which more women decamp the Republican Party, many Trump supporters see him as the stronger general-election candidate, particularly when facing Clinton.

Bob Sutton, chairman of the Broward County GOP Executive Committee in Florida, voiced confidence that Clinton would be easy to defeat in a debate — with a comment not likely to endear him to some female voters.

“I think when Donald Trump debates Hillary Clinton she’s going to go down like Monica Lewinsky,” he said.

Debbie Walsh, director of the Center for American Women and Politics at the Eagleton Institute of Politics at Rutgers University, said Clinton is poised to benefit from Trump’s unfavorable ratings and any gap between women and men voters. Clinton has been embracing her gender, something that could further endear her to women.

Clinton strategists think women are likely to be the key to a general-election victory for the former secretary of state, including independent and moderate Republican women motivated to vote for the first female president or because they are turned off by Trump or his chief rival, Cruz.

Clinton has built a 2016 campaign focused on issues of keen interest to female voters, including equal pay, health care and paid family leave. Her economic plan promises to “lift up participation in the workforce — especially for women.”

After deliberately playing down her gender in her loss in the 2008 race, Clinton now talks freely of her own experiences in the workplace and in politics. She often speaks of breaking “that highest, hardest glass ceiling” by being elected president, and she jokingly tells audiences that after more than 200 years and 44 male presidents, “It’s time.” She also gushes about being a grandmother and jokes about coloring her hair.

Walsh said women tend to vote not based on gender, but on sets of issues including economic security. Trump, she said, has been playing his own gender card, by trying to paint himself as the stereotypical strong — and male — presidential candidate.

But Ryan D. Enos, an associate professor of government at Harvard University, said it remains a real possibility that Clinton could lose votes because she is a woman.

“It’s not clear how much of that would be generated by Trump saying all this stuff and how much would be generated because some people don’t want to vote for a woman,” Enos said.

Enos said that if Trump is the Republican nominee, people could choose to vote for him because of party affiliation despite what he has said about women. And no matter who the Republican nominee is, if Clinton is the Democratic nominee, the election will probably be about gender.

“It’s unprecedented enough to have a woman running anyway. I think in a certain respect this would be an election about gender politics one way or the other,” he said.

Jose DelReal in Indianapolis and Emily Guskin in Washington contributed to this report.