Cell-mediated cytotoxicity (CMC) toward measles virus-infected cells was studied by a (51)Cr release assay with spleen cells from hamsters inoculated with measles virus (strain Lec) or control antigen and with spleen cells from normal hamsters. Spleen cells from measles virus-inoculated hamsters showed greater CMC toward infected than toward noninfected target cells (designated specific CMC). Specific CMC was maximal 7 days after virus inoculation and was declining by 9 to 10 days. Effector cells were present in a nonadherent cell population. Specific CMC was reduced after treatments of effector cells with antithymocyte serum plus complement. The decrease in cytotoxicity was greater toward infected target cells than toward noninfected target cells. Treatment of infected target cells with antimeasles serum did not increase specific CMC by effector cells from the majority of virus-inoculated hamsters. CMC toward infected target cells by normal spleen cells (natural killer cells) or spleen cells from hamsters inoculated with control antigen was approximately the same as, or more often less than, CMC toward noninfected target cells. Natural killer cells were present in a nonadherent cell population. Treatment of natural killer cells with antithymocyte serum plus complement caused a similar decrease in cytotoxicity toward both infected and noninfected target cells. This study demonstrated virus-specific cellular cytotoxicity of effector spleen cells from measles virus-inoculated hamsters. Although the data were compatible with T cells as the source of effector cells in the virus-specific CMC, definitive identification could not be made. Additional membrane markers for better characterization of hamster lymphocyte subpopulations are required.