A phase I double-blind trial was done to examine the safety and immunogenicity of a prototype synthetic human immunodeficiency virus type 1 MN strain (HIV-1MN) third variable region domain (V3) branched peptide vaccine in HIV-1-uninfected healthy adult volunteers. Subjects were randomly assigned to receive 20, 100, or 500 µg of vaccine or alum adjuvant control on days 0, 28, and 168. The vaccine was well-tolerated and appeared safe. Induction of binding antibody to V3 MN branched peptide was vaccine dose-related and was detectable in 9 of 10 subjects in the highest-vaccine-dose group. HIV-1MN-neutralizing antibody was detected after the third 500-µg dose in 8 of 10 subjects at the 90% neutralization end point. V3 MN peptide stimulated lymphocyteproliferation in 15 (75%)of 20 subjects after vaccination. In conclusion, this prototype vaccinewas safe and it induced humoral and cell-mediated immune responses.