First Lady Nancy Reagan, opening fire on a new target in the war on drugs, yesterday blamed the increasing narcotic-related deaths on the "casual user" and called on all Americans to be "absolutely unyielding and intolerant" in opposition to any use of illegal drugs.

"The casual user may think when he takes a line of cocaine or smokes a joint in the privacy of his nice condo, listening to his expensive stereo, that he's somehow not bothering anyone. But there is a trail of death and destruction that leads directly to his door," Reagan said.

"I'm saying that if you're a casual drug user, you are an accomplice to murder," Reagan said in a dramatic address kicking off the White House Conference for a Drug Free America.

Mandated by the Anti-Drug Abuse Act of 1986, the weeklong conference is bringing together drug abuse experts who will submit a final report and recommend solutions to the president and Congress this summer. It comes at a time when there are few signs that the drug crisis is waning: Drug-related killings are increasing nationally, even as the overall homicide rate has declined. Drug use and purity have increased, especially for cocaine, and new, initially inexpensive and more addictive drugs such as crack are sweeping the country.

Yesterday's opening session at the Omni Shoreham Hotel was more pep rally than policy conference, a gathering of believers punctuated by entertainers, films and buttons that said "Say Nope to Dope."

"They're preaching to the choir is what they're doing. It's a bunch of rah-rah," John P. Sulima, managing editor of The Drug Abuse Report, a trade journal, said of the session. "The real work will come later when they break into workshops."

But Reagan's speech set an urgent tone, calling for compassion and help for the drug addict and condemnation for the casual user. She illustrated her theme with these examples:

On Jan. 25, members of Colombia's powerful cocaine cartel allegedly rammed three Jeeps into the car of Attorney General Carlos Mauro Hoyos, then sprayed it with machine gun bullets, shattering Hoyos' skull and killing his two bodyguards.

"And . . . the people who casually use cocaine are responsible because their money bought those bullets," she said. "They provided the high stakes that murdered those men plus hundreds of others in Colombia, including supreme court justices, 21 judges handling drug cases and scores of policemen and soldiers."

On Feb. 7, 1985, three months after he had helped uncover and destroy a 10,000-acre marijuana farm in Mexico, Drug Enforcement Administration Special Agent Enrique Camarena was kidnaped, tortured and beaten to death, allegedly by marijuana traffickers. "And this country's casual marijuana users cannot escape responsibility for their fellow American's death because they, in effect, bought the tools for his torture," Reagan said.

On Jan. 4, 1987, 20-year-old Christy Johnson of Potomac and 15 other persons died when a Conrail locomotive crashed into an Amtrak train near Baltimore. The Conrail engineer and brakeman later acknowledged that they shared a marijuana cigarette before the crash, which also injured 175 people.

"Now don't tell the Johnsons that casual drug use is a victimless crime," Reagan said. "Don't try to tell the Johnsons that drugs hurt no one but the user."

Apologizing to the crowd of about 800 for the brutality of the stories she recounted, Reagan told of the killings of four young men in rural Indiana and the wounding of their mother by four other men who were high on drugs. And she told of the April 3, 1982, slaying of Stephanie Roper, a 22-year-old Frostburg College senior from rural Prince George's County, who was raped, shot and set afire.

Reagan, who has spent much of her seven years as first lady campaigning against drugs, vowed to continue her work in California after her husband leaves office. "You can't get rid of me," she said to a standing ovation.