We have found numerous and exquisite homologies between the interleukin-2 (IL-2)-activated killing systems of rhesus monkeys and humans. Lymphocytes with high oncolytic and proliferative activity were generated from peripheral blood, spleen, and bone marrow of monkeys after culture with IL-2. The distribution of lymphocyte subsets in IL-2 cultures closely paralleled that seen in humans, including a decrease in CD4+ and increase in CD8+, CD38+, and CD25+ lymphocytes and an increase in density of CD2 molecules. We also describe three distinct subsets of monkey lymphocytes, CD16+,56-, CD16+,56+"dim", and CD16-,56+"bright", and show that the CD56+"bright" subset is substantially increased (to as high as 79%) after IL-2 activation. Furthermore, as in humans, the cells with oncolytic activity were characterized as CD56+, CD16+/-, and CD8+. This strong homology with humans indicates that the rhesus monkey may be a valuable preclinical model for evaluation of therapeutically relevant biological response modifiers.