While Dr. Soffritti's methods have drawn some criticism, the Ramazzini cancer lab, which is financed by private bank foundations, governments and 17,000 individual members, has earned considerable credibility since it was founded in 1971 for its pioneering research on chemicals. It was the first research body to do studies showing that vinyl chloride and the gasoline additive methyl tertiary-butyl ether, or M.T.B.E., are carcinogenic, research that eventually encouraged the United States to strictly regulate vinyl chloride and that led 21 states to ban M.T.B.E.

Dr. Soffritti said he was inspired to look at aspartame because of what he calls "inadequacies" in the cancer studies done by Searle in the 1970's. He said that those studies did not involve large-enough numbers of rats and did not allow them to live long enough to develop cancer.

The Ramazzini study was conducted with 1,900 rats, as opposed to the 280 to 688 rodents used in Searle's studies, and the rats lived for up to three years instead of being sacrificed after two, which is the human equivalent of age 53. "Cancer is a disease of the third part of life," Dr. Soffritti said. "You have 75 percent of cancer diagnoses for people who are 55 years old or older. So if you truncate the experiments at 110 weeks and the rats are supposed to survive until 150 to 160 weeks, it means you avoid the development of cancer at the time when cancer would be starting to arise."

Others have also challenged Searle's studies. Documents from the F.D.A. and records from the Federal Register indicate that, in the years before the F.D.A. approved aspartame, the agency had serious concerns about the accuracy and credibility of Searle's aspartame studies. From 1977 to 1985 -- during much of the approval process -- Searle was headed by Donald H. Rumsfeld, who is now the secretary of defense; Searle was acquired by Monsanto in 1985. Monsanto later spun Searle's assets out into two companies: Merisant, which owns the brands Equal and Canderel, and NutraSweet, which is owned by J. W. Childs Equity Partners, an investment firm in Boston.

A 1976 report from an F.D.A. task force, for example, found that Searle's studies on aspartame and several of the company's pharmaceutical drugs were "poorly conceived, carelessly executed, or inaccurately analyzed or reported." It cited what it called a lack of training by the scientists analyzing tissue samples, a "substantial" loss of information because of tissue decomposition and inadequate monitoring of feeding doses.

In response to the report, the F.D.A. asked the Justice Department to open a grand jury investigation into whether two of Searle's aspartame studies had been falsified or were incomplete. In a 33-page letter in 1977, Richard A. Merrill, the F.D.A.'s chief counsel at the time, recommended to Samuel K. Skinner, then the United States attorney for the Northern District of Illinois, that a grand jury investigate the company, which was based in the Chicago suburb of Skokie, for "concealing material facts and making false statements in reports of animal studies conducted to establish the safety of the drug Aldactone and the food additive aspartame."

A grand jury was never convened, however. Shortly after the letter was sent, Mr. Skinner left the Justice Department to join Sidley & Austin, a law firm that represented Searle. After 12 years at that firm, now Sidley, Austin, Brown & Wood, Mr. Skinner was appointed to be President George H. W. Bush's transportation secretary; later he became his chief of staff. In 1978, a year and half after Mr. Skinner left the United States attorney's office in Chicago, his deputy, William F. Conlon, also left to work at Sidley & Austin.