Rabbit lymphoid cells from spleen, peripheral blood, and peritoneal cavity lacked killer (K)-cell activity against cell lines of rabbit and human origin, including virus-infected human tumor cells. This lack of activity was not affected by antibody concentration, source of antibodies, effector/target cell ratio, or length of assay. Rabbit leukocytes, however, were capable of lysing antibody-coated chicken erythrocytes. Hamster leukocytes, serving as a known source of K cells, mediated antibody-dependent cellular cytotoxicity against all targets. EA-rosette assays and mixed effector cell competition tests suggested a deficiency in rabbit K-cell activity which is not a result of an inherent lack of Fc receptor-positive cells or of some suppressor mechanism operating in the rabbit cell populations. Our data support the concept that antibody-dependent cellular cytotoxicity may not be a significant in vivo immune mechanism in certain species.