By subcutaneous inoculation of SHIV(KU-2) in the hands of macaques, we developed a model of human immunodeficiency virus type-1 (HIV-1) occupational infection due to needle-stick injury and used the model to determine whether neutralizing serum to SHIV administered before or after virus inoculation could either prevent or abort infection, respectively. Six rhesus macaques were given 15 ml/kg pooled anti-SHIV plasma and challenged 24 hr later with approximately 300 animal infectious doses of SHIV(KU-2), subcutaneously. Three of the six macaques completely resisted infection with SHIV(KU-2). A fourth animal failed to yield infectious virus, but DNA extracted from its peripheral blood mononuclear cells (PBMC) and lymph nodes had viral sequences. Partial resistance was noted in the other two animals because virus recovery was delayed compared with the control animals. In contrast, six of six macaques given the same dose of anti-SHIV plasma 18 hr after exposure to virus became infected, as did two of two macaques given anti-SHIV plasma only 2 hr after exposure to virus. Our results suggest that neutralizing antibodies may have a prophylactic but not a therapeutic role in HIV-1 infections.