The Supreme Court was highly skeptical yesterday of the Food and Drug Administration's claim that it can regulate cigarettes, suggesting a major setback for the Clinton administration's efforts to restrain the tobacco industry.

During one of the most vigorous oral arguments at the court in months, the justices suggested by their questions that they were almost certain to invalidate the FDA's watershed effort to regulate the nicotine in cigarettes and smokeless tobacco as a drug.

Justices across the ideological spectrum homed in on weaknesses in the government's case, notably that the FDA had for decades said it lacked the authority to regulate tobacco and that the agency's historical mandate is to oversee items intended to make people healthier. "It just doesn't fit," said Justice Sandra Day O'Connor, noting that the FDA is charged with ensuring that drugs are safe and effective and "it strains credibility" to claim cigarettes are safe.

Yesterday's case arises against a backdrop of escalating legal attacks on Big Tobacco over the past several years, including a recent Florida class action verdict that could cost the industry billions of dollars and a massive new lawsuit filed against the industry by the Justice Department.

The dispute before the court began in 1996, when the FDA declared it could regulate the nicotine in tobacco products and proposed rules to restrict their sale and marketing to young people. The agency drew this authority from the 1938 Food, Drug and Cosmetic Act, which gave the FDA jurisdiction over drugs and devices "intended to affect the structure or any function of the body." The agency asserted that nicotine's effects on the body were clearly "intended" by cigarette makers.

But tobacco companies challenged the FDA's proposed restrictions, and last year the U.S. Court of Appeals for the 4th Circuit ruled that the agency lacked authority over tobacco, saying that such power lies with Congress alone.

In the government's appeal yesterday, Solicitor General Seth P. Waxman compared the effects of nicotine in cigarettes to other drugs that are addictive or work as stimulants, sedatives or appetite suppressants.

But the justices' questions quickly put Waxman on the defensive. Chief Justice William H. Rehnquist challenged Waxman's claim that it was only in the 1990s that the FDA found the scientific evidence that cigarettes were addictive and harmful, pointing to a 1964 surgeon general's report and other earlier findings about tobacco's health effects.

A clearly frustrated Waxman asserted at one point that Congress could not have intended the "ridiculous" public health situation of protecting a drug from regulation because evidence about its effects were only recently determined. He described tobacco as "the only product ingested in the body that is regulated and inspected by no agency and yet is so dangerous."

Richard M. Cooper, the attorney representing Brown and Williamson Corp. and other tobacco companies, contended that Congress never meant to delegate authority over cigarettes to any agency, but rather sought to regulate them through a series of tobacco-specific statutes, such as a 1965 package labeling law. He also emphasized that cigarette makers do not promise specific health effects from their products, as do the manufacturers of other drugs and items that the FDA is charged with overseeing. "The FDA comes in when there is a claim of a health benefit," he said.

Justice David H. Souter seemed receptive to these arguments, and described his difficulty with the government's position as "global."

But Justice Stephen G. Breyer was less clearly persuaded, noting that despite the lack of explicit health claims by cigarette manufacturers, "The unusual thing here is that we do have a product that everyone knows what it does."

After the arguments, on the front steps of the Supreme Court building, former FDA commissioner David A. Kessler emphasized that the agency was thwarted in regulating cigarettes before the 1990s because "we didn't have key evidence until 1994." He cited the troves of newly obtained internal company documents, such as the 1963 memo from the top lawyer at Brown and Williamson that said "we are, then, in the business of selling nicotine, an addictive drug."

But Charles Blixt, executive vice president and general counsel of R.J. Reynolds Co., countered that the debate actually comes down to a choice about who will decide how tobacco will be regulated: "Is it the Congress, or is it a single unelected bureaucrat?"

A ruling in the case of Food and Drug Administration v. Brown and Williamson is expected next spring.

Staff writer John Schwartz contributed to this report.