Inbred strains of mice differ markedly in levels of natural killer (NK) cytotoxic activity. BPS mice normally have very low spleen cell NK activity. However, their NK activity can be significantly augmented with the use of interferon inducer, which suggests that this basic low reactivity is not a result of low numbers of precursor cells or defects in the lytic mechanism. Normally, their spleens contain suppressor cells, as evidenced by the ability of BPS spleen cells to inhibit in vitro the NK activity of spleen cells from high-responder strains of mice. Cells responsible for the suppression are located in the dense fraction after separation in Ficoll-Hypaque and are nylon wool-adherent. Studies on the kinetics of inhibition indicate that the mechanism of inhibition is not merely competition for target-binding sites. Although these suppressor cells can act on mature NK effectors in vitro, their activity in vivo may be more complex, since mature BPS NK effectors are not revealed when the suppressors are removed.