Spleens of normal young mice of certain genotypes contain lymphocytes that can kill strain A-derived YAC-1 and some other in vitro-grown Moloney lymphoma lines in a 51Cr-release cytotoxic test. We have previously shown that mouse strains can be classified as high or low reactors in this test. F(1) hybrids between low- and high-reactive strains are high-reactive. In the present study, strain-A mice and eight different A F(1) hybrids were tested in parallel for their spleen-cell-mediated killing effect in vitro and their ability to reject graded numbers of YAC ascites or in vitro cultivated cells in vivo. There was a clear correlation between in vitro cytotoxicity and in vivo rejection in all tested genotypes. In segregating (A times C57Bl) times A backcross mice, in vivo rejection of YAC cells was H-2 linked. This is in line with the earlier backcross analysis of the in vitro cytotoxicity, suggesting a polygenic control with at least one H-2 linked factor.