Using our recently developed target system model of env gene-transfected cells for gp120/41-specific antibody-dependent cellular cytotoxicity (ADCC) assays, we evaluated the ADCC effector function of the peripheral blood mononuclear cells (PBMC) in 39 human immunodeficiency virus type 1 (HIV-1)-infected individuals. The natural killer (NK) activity of the PBMC from these individuals against K562 was also determined. A significant positive correlation (p < or = 0.05, r = 0.37) was found between these two activities. On the basis of our data, we built a regression equation for the two activities whereby the ADCC effector function of PBMC of an HIV-infected individual can be predicted from their NK activity. We also found that the endpoint titer of a given serum for ADCC-mediating antibodies in the ADCC assay varied depending on the NK activity of the effector cells used: The effectors with high NK activity tended to give higher titers as compared with the effectors with low NK activity. To our knowledge, this is the first formal documentation of the existence of a positive correlation between the ADCC and NK activities of the PBMC. It also shows that the ADCC titer of serum in ADCC assay may vary depending on the NK activity of the effector cells used. This observation underscores an important variable of ADCC assays. Using our statistical model, one can predict the ADCC effector function of the PBMC from HIV-infected individuals from their NK activity and thus help clarify the role of this important immune response in HIV infection and AIDS prognosis.