Haptenated chicken erythrocytes, anti-hapten antibodies and normal spleen cells were used for a sutdy of parameters of antibody-dependent cell-mediated cytotoxicity (ADCC). Anti-hapten antibody was introduced to the reaction either bound to the target cells (sensitization) or to the effector cells (arming). Our data suggest that the same effector cells and the same antibodies were responsible for both types of reactions. More antibody was required for arming (ca. 1 ng/ml) than for sensitization (ca. 10 pg/ml). Antibodies of several mammalian species could cooperate in ADCC with human, rat, or guinea pig spleen effector cells, but fowl antibodies were inefficient in the arming of mammalian effector cells. Rat and human spleen cells were powerful effector cells whereas guinea pig, rabbit, and mouse spleens yielded weakly cytotoxic suspensions. Rabbit antibodies, on the other hand, were efficient, but rat antibodies were less efficient in ADCC. Mouse and guinea pig antibodies appear to take an intermediate position. Our data suggest that ADCC effector cells of the spleen contain phagocytic and nonphagocytic cells, and the non-phagocytic effector cells still constitute a heterogenous population.