Human effector cell function in ADCC reactions was studied as a result of observations showing discrepant ADCC reactivities among different effector cell populations. Effector cells prepared from ten blood donors were tested individually and as a pool against a battery of nine antisera-target cell combinations in an 11-x-9 matrix. The results identified individuals with weak, intermediate, and strong effector cell functions; however, there was a wide range of ADCC reactivity by each person's effector cells against the nine targets. No single antibody-target cell combination was consistently subjected to the least kill or greatest kill by the different effector cell preparations. Pooled effector cell responses were found to be weaker than expected. There was no relationship of age or sex with effector cell function, but a trend was noted for strong and weak reactions to be associated with HLA-DR7 and DR1, respectively. Neither the sharing of HLA antigens between effector and target cells nor self ADCC reactivity could account for the variations in effector cell function. Exploratory principal components factor analysis suggested that recognition of antibody-target cell combinations by effector cells was represented by three major groupings. These data collectively indicate the existence of an allorestrictive Fc receptor recognition step in ADCC responses.