New York researchers are leading the most ambitious smallpox study to date, examining how the vaccine responds in people born from the late 1920s through the early 1970s, government health officials confirmed yesterday.

Nearly 1,000 people are being sought as volunteers for the nationwide project, in which they will receive either a dilution of the live-virus vaccine or a full-strength inoculation.

The study is expected to be the largest in a series sponsored by the federal government in which the freeze-dried vaccine known as Dryvax is being administered. Some Dryvax stocks are more than 40 years old.

A spokesman for the National Institutes of Health said yesterday that the study, the second in a series of the investigations, is designed to give scientists a sense of how people previously vaccinated against smallpox respond.

The last case of smallpox in the United States occurred in 1949, and routine vaccinations against it stopped in 1970.

Although the disease was declared eradicated globally in 1980, U.S. defense experts believe terrorist factions might have replicated the virus.

Dr. John Treanor, associate professor of medicine at the University of Rochester in New York and the study's lead investigator, said it's likely that people who were vaccinated in the past - even as long ago as the 1920s and 1930s - might have residual immunity.

But while that defense might not be strong enough to fight off a smallpox infection, it could prove hardy enough, Treanor said, for people's immune systems to fight off diluted versions of the vaccine.

If that were to occur, those vaccinated would not be protected against smallpox.

To know for certain - and to know whether some people need full-strength inoculations - Treanor said researchers now are seeking a broad range of ages for the clinical trial.

"It's likely the body may tamp down the diluted vaccine; we don't know. The subjects in this study are people who were vaccinated as children and for some people that may have been 30, 40, 50 years ago.

"We are enrolling people from about 32 or so, all the way up to age 75," Treanor said.

Treanor also said preliminary discussions have begun on ways to deactivate vaccinia, the live virus used in the smallpox vaccine.

This possibly could expand the number of people who can be vaccinated against the highly contagious and potentially fatal infection.

Currently, the live-virus immunization cannot be given to anyone with an immune system disorder.

Government health officials say the smallpox vaccine studies are part of stepped-up preparedness efforts in the event of a biological attack.

The clinical trials afford doctors knowledge of how to administer the vaccine and how various age groups respond to it.

A clinical trial in which children are to be inoculated is on hold pending the government's unprecedented solicitation of public opinion about the ethics of vaccinating children without an apparent threat of smallpox.

Delthia Ricks is a reporter for Newsday, a Tribune Publishing newspaper.