This study confirms the presence of detectable antibody-dependent cell-mediated cytotoxicity (ADCC) towards both HTLV-I- and HIV-1-infected cell lines, mediated by normal donor peripheral blood mononuclear cells and either by antibody from adult T-cell lymphoma and tropical spastic paraparesis patients (HTLV-I) or by antibody from sera of patients with persistent generalized lymphadenopathy, AIDS-related complex, AIDS and asymptomatic patients seropositive for HIV-1 infection. A comparison of ADCC towards these two retroviruses, under carefully controlled laboratory conditions, indicates major differences between the capacity of HTLV-I-seropositive sera and HIV-1-seropositive sera to mediate ADCC. In all cases, HIV sera showed low-titre ADCC, in contrast to the high titre (greater than 1:800,000) ADCC mediated by HTLV-I-positive sera. Both sets of sera showed the prozone phenomenon, and heat inactivation may abolish ADCC towards HIV-1-infected cells. Quantitation of surface antigen expression on HTLV-I- and HIV-1-infected cell lines indicated the presence of easily detectable amounts of virus-specific antigen. We conclude that, in contrast to some previous reports, ADCC mediated by HIV-1-specific immunoglobulin G (IgG) antibody is rather weak and of low titre when compared with HTLV-I ADCC. This is true for all cell lines and HIV-1 virus isolate combinations tested.