Antibody-dependent cellular cytotoxicity (ADCC) is an important antiviral effector mechanism. However, its role, as well as the functional integrity of the ADCC-effector cells in HIV infections, is not well understood. For studying gp120/41-specific ADCC, we recently developed a virus-free target cell system, using a natural killer (NK) cell activity-resistant human lymphoid cell line of B lineage, which was transfected with theenvgene of the human immunodeficiency virus type 1 (HIV-1); gp120/41-expressing cell clones were thus selected. In this study, these gp120/41-expressing cloned cells were used as targets in a gp120/41-specific ADCC assay for (a) examining the functional integrity of ADCC-effector cells from HIV-seropositive individuals, and (b) titrating the sera of these individuals for gp120/41-specific. ADCC-mediating antibodies. Our data indicate for the first time that the percentage of sera positive for ADCC-mediating antibodies to gp120/41 is higher in individuals with CD4 counts ±400 and ±200/mm3. The individuals with CD4 counts <200/mm3were found to have the lowest titers of these antibodies in their sera. The ADCC-effector function of the peripheral blood mononuclear cells (PBMC) of HIV-infected individuals was significantly (p< 0.05) reduced as compared to the PBMC from healthy, HIV-seronegative individuals. Further, human recombinant IL2 and interferon-γ were found to exert a significant (p< 0.05) enhancing effect on ADCC mediated by PBMC from these HIV-infected individuals. We also show that two virus neutralizing, gp120-specific mouse monoclonal antibodies 0.5β and 902 were unable to mediate ADCC as well as to block the ADCC mediated by the AIDS patients' sera. Further, these results suggest that the present gp120/41-expressing target cell system might prove very useful in conducting large-scale studies on both gp120/41-specific ADCC-effector function of peripheral blood mononuclear cells and ADCC-mediating antibody responses in different types of HIV-positive individuals.