U.S. public health officials are weighing whether to require domestic travelers to show proof of a negative coronavirus test before boarding their flights, drawing fierce opposition from airlines, labor unions and lawmakers but underscoring the severity of the pandemic and difficult trade-offs involved with trying to subdue it.

In an interview broadcast Sunday, Transportation Secretary Pete Buttigieg told Axios on HBO there is an “active conversation” with the Centers for Disease Control and Prevention about whether to require coronavirus testing for domestic flights. Pressed Monday in a CNN interview on the likelihood of that happening, Buttigieg said “the CDC is looking at all its options.”

The federal government already requires international travelers to be tested before they board flights to the United States — a mandate that drew praise from many in the aviation industry. But requiring tests for domestic travelers raises a different set of challenges for the administration.

While Buttigieg said such testing is appropriate for international travel, he told CNN, “the domestic picture is very different,’’ adding, “there’s got to be common sense, medicine and science really driving this.”

He acknowledged aggressive pushback from the travel industry. In response to a letter last month by industry groups saying the testing requirement would siphon public health resources from more vulnerable populations, Buttigieg told CNN, “I think they’re raising very valid points, and those points will, I know, be taken very seriously.”

A testing requirement would mark an aggressive effort to disrupt one aspect of the disease’s spread. While government officials have emphasized the power of masks while vaccinations reach more people, millions of Americans continue to travel by air each week. The spread of a more contagious variant and a second mutation that somewhat diminishes the effectiveness of a vaccine have added a level of urgency and helped prompt consideration of additional public health measures, including preflight testing.

“As part of our close monitoring of the pandemic and in particular the emerging variants, we will continue to review public health options for containing and mitigating spread of the virus,” the CDC said in a statement Tuesday.

Officials are weighing health concerns against the economic impact a mandate might have on an industry already hobbled by the pandemic. Carriers have received more than $60 billion in government grants and loans, while unions are lobbying for an additional $15 billion in support. American and United are among the carriers that recently announced they might have to furlough more than 27,000 employees at the end of March if federal support is not extended.

David Freedman, an emeritus professor of infectious diseases at the University of Alabama at Birmingham, said testing might particularly help to slow the spread of the virus variant that was first discovered in South Africa and could give people more time to get vaccinated as other variants take hold.

While Freedman questioned the effectiveness of requiring a test three days before a flight, the rule for international travelers, he said rapid tests could have a meaningful effect.

Mara Aspinall, a biomedical diagnostics professor at Arizona State University and adviser to the Rockefeller Foundation, said the United States needs to do what it can to make each mode of transportation as safe as possible.

“Testing is a critical layer,” she said. “It’s not just protection, it’s information. Many other layers are important and critical, but testing can help us isolate those who are positive even when they are completely asymptomatic.”

There may be limits to how effective a domestic program could be, officials said.

“Since you can drive to most states without a single checkpoint, I think it is a fair argument that a testing requirement before domestic flights would probably have a lesser impact than it would for international travel, except for Hawaii which already requires a negative test to avoid quarantine,” said Henry Wu, an associate professor at the Emory University School of Medicine in Atlanta and director of the Emory TravelWell Center.

Ed Bastian, chief executive of Delta Air Lines, said Tuesday on CNN that a testing requirement is a “horrible idea” and argued it would not make domestic travel safer.

He is backed by a coalition of aviation groups, which released a four-page document outlining reasons requiring travelers in the United States to test negative before they board a flight would be ill-advised.

The coalition, which includes the trade group Airlines for America and unions representing pilots and flight attendants, said a requirement is not “scalable, feasible or effective” and would lead to “further job losses without producing meaningful public health benefits.”

Lawmakers, too, have expressed reservations about such a mandate.

At a hearing last week, Rep. Peter A. DeFazio (D-Ore.), chairman of the House Transportation and Infrastructure Committee, raised broad questions about the practicality and effectiveness of a domestic testing requirement.

He noted the country already is facing a shortfall in needed coronavirus tests. Requiring them before flights would mean increasing testing capacity nationwide by about half, he said during a hearing Thursday on worker safety.

Sara Nelson, president of the Association of Flight Attendants-CWA, said a preflight testing requirement would devastate the airline industry.

“Isolating the airline industry and not doing the same thing for mass transit or doing this at grocery stores or restaurants doesn’t make any sense as we have community spread,” she said.

David Michaels, former chief of the Occupational Safety and Health Administration under President Barack Obama, said the possible benefits of such testing would be outweighed by the costs.

“We know how to protect workers and passengers on planes: Masking, improved ventilation and filtration, and distancing [are] very effective,” he said.

Even if the Biden administration moves forward with a domestic testing requirement, experts say, it will be important to remind the public that testing is not a panacea.

“I think regular testing of any population at high risk for infection could help control this pandemic. However, we need to be mindful of our testing resources and not giving travelers an impression that they can relax their precautions if they test negative,” Wu said. “No single requirement or intervention is going to control this pandemic.”