In 1981, a hepatitis B virus vaccine demonstration project was conducted in 1630 Yupik Eskimos in southwest Alaska. Levels of antibody to hepatitis B surface antigen and markers for hepatitis B virus infection in vaccinees were monitored yearly for 5 years. After 5 years of follow-up, 19% of those who initially had an immune response to vaccine of 10 sample ratio units or greater subsequently had levels of antibody to hepatitis B surface antigen lower than 10 sample ratio units. During the 5 years after the first dose of vaccine, in three responders and one person with an antibody to hepatitis B surface antigen response lower than 10 sample ratio units, antibody to hepatitis B core antigen developed, and the level of antibody to hepatitis B surface antigen was boosted. Hepatitis B surface antigen did not develop in any subjects, and none had clinical hepatitis. In the 5 years following the demonstration project, the annual incidence of hepatitis B virus infection decreased from 50 cases per 1000 population before the vaccine trial to 0.45 per 1000.