The safety and immunogenicity of HIV-1(MN) recombinant gp160 (MN rgp160) vaccine in healthy, uninfected volunteers was tested in a double-blind study with a factorial design. By random assignment, 20 volunteers received three 200 μg doses of MN rgp160 and four volunteers received placebo at day 0, 28 and 168 or 0, 56, and 224. Of the 24 volunteers, 16 received 200 μg or 800 μg of MN rgp160 and two received placebo at day 532 (month 18). The vaccine was safe. It induced T cell memory measured by Th1 cytokine production and lymphocyte proliferation and serum anti-MN rgp160 IgG (all subclasses) and IgA antibodies. Fifteen of 20 vaccinees developed neutralizing antibody. The regimen including immunizations on days 0, 28, and 168 followed by the 800 μg fourth dose was most immunogenic.