A randomized, double-blind clinical trial of plasma-derived and DNA recombinant hepatitis B virus vaccines was conducted in 186 homosexual men. Nine months after the immunization series (three doses) began, the seroconversion rate in the plasma vaccine group was 88% (68/77); this was significantly higher than the 74% (60/81) response rate of the recombinant vaccine group. Men positive for antibody to the human immunodeficiency virus (HIV) had a considerably higher nonresponse rate to either vaccine than expected in non-HIV-infected homosexual men. The odds ratios of nonresponse to hepatitis B virus vaccine for HIV-seropositive vs HIV-seronegative subjects were 12.0 (95% confidence interval, 1.7 to 89.3) and 13.6 (95% confidence interval, 2.3 to 148.3) for the plasma and DNA recombinant vaccines, respectively.