A yeast-derived recombinant DNA vaccine against hepatitis B was administered to 314 active homosexual men lacking serum markers for hepatitis B virus. Volunteers were vaccinated intramuscularly in the deltoid region at 0, 1, and 6 months with either a 20- or 40-micrograms dose per injection. Serologic tests for syphilis and human immunodeficiency virus were positive in 3.2% and 2.0%, respectively. The overall seroconversion rates for anti-HBs were 35%, 97%, and 98% after the first, second, and third injection, respectively. The geometric mean titres of anti-HBs antibodies at 7 months were 955 IU/l and 2541 IU/l, for the 20 and 40 micrograms doses, respectively. Among 183 completely vaccinated subjects, 97% had an anti-HBs titre greater than 10 IU/l. Tolerance of the vaccine was excellent. Among the 183 subjects followed up for at least 7 months, two volunteers developed HBsAg and anti-HBc within one month of the first vaccine injection and one anti-HBc just before the third dose of vaccine. However, no subject experienced clinical hepatitis or ALT elevations.