The ability of autoimmune New Zealand mice and control mice to suppress the generation of cytotoxic lymphocytes was studied. These experiments demonstrated that allosensitized spleen cells from both 1 and 6-month old female NZB,NZW, and NZB/NZW F1 mice or culture supernatants of such cells, could supress the in vitro generation of cytotoxic lymphocytes. In addition, the cytotoxic lymphocyte responses of NZW and NZB/NZW F1 mice were suppressed by allosensitized cells and their culture supernatants. In contrast, cytotoxic lymphocyte responses of NZB, as well as CBA/J and CBA/N mice, although readily suppressed by allosensitized spleen cells, were resistant to suppression by the culture supernatants of these allosensitized cells. To investigate further NZB and CBA resistance to cytotoxic lymphocyte suppressor factor(s), F1 hybrids of resistant X susceptible and resistant X resistant strains were studied. F1 hybrids of strains suppressed by culture supernatant suppression were all suppressed, demonstrating suppression to be a dominant phenotypic trait. F1 hybrids of 2 strains resistant to supernatant suppression were not suppressed; thus, resistance was recessive without gene complemenation. Furthermore, all stains resistant to suppression by culture supernatants were suppressed by the allosensitized cells. This cell-supernatant dichotomy suggests that allosensitized spleen cells can suppress several different steps in a cytotoxic immune response.