The cytotoxic efficacy of a heteroconjugate antibody composed of OKT3 cross-linked to a broadly reactive antibody directed against the GPGRAF sequence of the gp120 V3 region has been characterized. The heteroconjugate antibody could completely inhibit viral replication of both the IIIB and MN isolates of human immunodeficiency virus (HIV) at concentrations as low as 0.5 ng/rnl, At an antibody concentration of 1 µg/ml, heteroconjugate-mediated cytotoxicity occurred at effector-to-target ratios as low as 0.006: 1. Eight different HIV isolates were tested for in vitro inhibition by the anti-V3-0KT3 conjugate, and all but one were completely inhibited for at least 7 days. These results indicate that heteroconjugate antibodies are a potent, effective means by which HIV-infected cells can be killed and viral replication suppressed.