The search for what makes a man a man, one of the abiding puzzles of human genetics, may be over.

In a paper published in today's issue of the scientific journal Nature, a group of British scientists reports that it has identified a single gene that appears to set in motion a cascade of events that turn a fertilized egg into a male. In the absence of the gene, researchers say, the embryo would become female.

The findings are not yet conclusive. According to the scientists who conducted the research, final proof awaits the outcome of experiments on mice. In addition, another paper published in the same issue of Nature suggests that while the gene identified by the British team appears to be critical in determining maleness, there is some evidence that two or three other genes may be necessary for fully normal maleness.

But after 30 years of intensive and often frustrating detective work by geneticists, the gene appears to be the most promising candidate discovered to account for the anatomical and perhaps even some behavioral differences between the sexes. By better explaining the determinants of human development, it also appears to open the door to better understanding and perhaps treatment of some causes of infertility. "This discovery is likely to be a landmark that will be remembered for a long time in the development of science," Nature editor John Maddox told a news conference in London yesterday.

The researchers named the gene SRY, for "Sex-determining Region of the Y chromosome." The Y chromosome and the X chromosome have long been known to contain the gene or genes that determine sex. Each human has 46 chromosomes in each cell, containing an estimated 50,000 to 100,000 genes necessary for human life. Females have two X chromosomes. Males have one X and one Y.

Although the presence of the Y chromosome is clearly the factor that differentiates a man from a woman, not all of the thousands of genes that lie on it are involved in determining sex. As early as 1966, for example, scientists had found men with two X chromosomes. This apparent defiance of genetic dogma was resolved within the last few years when researchers discovered that these XX males had, by a rare genetic accident, a tiny portion of a Y chromosome attached to one of their Xs. These individuals, who look and function unequivocally as men, possessed just one half of one percent of the genes that normally lie on the Y chromosome.

This showed that the trigger that determines whether an embryo becomes a boy or a girl must lie within that tiny part of the Y carried by XX males.

But which was the exact gene? In two papers in the current issue of Nature, two teams of London researchers led by Andrew H. Sinclair and Robin Lovell-Badge argue that the culprit is the SRY gene. Their evidence comes from mice, whose sex is determined by X and Y chromosomes very similar to those of humans. SRY, the researchers found, is activated in mice at just the time when the development of male and female mouse embryos diverges onto different paths.

At the same time, the researchers had the good fortune to find a mouse with both an X and Y chromosome that, because of a mutation, lacked the critical SRY gene. The XY combination meant it should have been male but it was female.

According to an editorial in Nature written by Anne McLaren, a geneticist at University College, London, "none of this evidence establishes conclusively that SRY" is the maleness gene. She suggests that to prove the hypothesis scientists will have to insert the SRY gene into the genome of an XX mouse and see if it turns out male.

Another paper published in Nature also urges caution in accepting the SRY gene as sufficient to cause normal maleness. David Page, a geneticist at the Whitehead Institute in Cambridge, Mass., who announced in 1987 that he might have found the maleness gene but was proven wrong, cites previous research that more than one gene may be needed. Page said the research shows that XX humans who also carried a tiny snippet of the Y containing the SRY gene but little else were only ambiguously male, lacking, for example, fully developed male genitalia.

"These are not subtle differences," Page said. "There is a strong circumstantial case that {SRY} is involved in sex determination. But the fact is, it isn't associated with complete masculinization, suggesting that there might be one or two or even more other genes involved. . . . This is an important landmark, but we still have a long way to go."