Monoclonal antibody BAT123 was passively transferred into SCID mice reconstituted with human peripheral blood lymphocytes (hu-PBL-SCID) to study passive antibody protection against human immunodeficiency virus type 1 (HIV-1) infection. BAT123 is specific for the third variable loop of the gp120 of HIV-1LAI. Animals were protected against subsequent infection with LAI strain, but not other virus strains, when BAT123 (1 mg/kg; 25 micrograms/mouse) was given 1 h before virus inoculation. This resulted in a peak serum concentration of 16 micrograms/mL of the antibody, which should be easily attainable in humans. In addition, postexposure protection was observed when the antibody was given within 4 h of virus inoculation. No therapeutic effect was observed, however, when BAT123 was administered after infection had been established. These results indicate that passive antibody prophylaxis against HIV-1 infection may be possible in certain clinical situations.