Recombinant gp160 derived from human immunodeficiency virus type 1 (HIV-1)IIIB and produced in mammalian tissue culture cells using a vaccinia virus expression system (rgp160-mam) was evaluated as a vaccine in combination with alum and deoxycholate adjuvant. Sixty low-risk, uninfected subjects received 12.5 micrograms, 50.0 micrograms, or adjuvant control at 0, 1, 6, and 12 months in a randomized, double-blind dose-escalation study. A single injection of 200 micrograms of vaccine was given at 18 months in an open study to 9 vaccines who had received 50 micrograms. The vaccine was safe. Six of 16 subjects receiving 50 micrograms developed neutralizing antibody to HIV-1IIIB. Seven of the 9 boosted with 200 micrograms of vaccine at 18 months developed neutralizing antibodies. Lymphocyte proliferation to rgp160-mam and baculovirus-derived rgp160 and rgp120 was induced in both groups (12.5 and 50.0 micrograms) and appeared after the first dose. Further studies with higher doses of rgp160-mam and vaccines derived from other strains of HIV-1 are warranted.