SummaryTumors induced in hybrid mice between C57BL/10Sn and its isogenic resistant (IR) strains (shown to be coisogenic) were used for the study of histocompatibility variants in mouse tumor cells. In previous studies A/Sn and its IR strains have been used. These were later shown to be not coisogenic or homozygous. Both hybrid sarcomas and lymphomas were used. Unlike A/Sn and its IR strains, all sarcomas and lymphomas tested produced variants when transplanted in the parental strains. Again, for any hybrid combination, no parental strain was favored for variant production. The number of variants produced deviated from generation to generation. Different sublines of the same tumor also gave different numbers of variants. The number of variants decreased with reduction in inoculum. This indicates that the pre-existence of certain cell clones in the initial inoculum is important in variant production. The variants were highly specific and stable. Homozygous tumors, however, failed to produce true variants. Cytological studies showed that the variants had larger numbers of cells at hyperdiploidy and triploidy than the original tumor. In view of the cytological instability and the difference in transplantation behavior of hybrid tumors, it is concluded that tumors are not good material for the study of somatic mutations. Embryonic tissue was also investigated for histocompatibility changes. As large numbers of cells were required to establish a growth in adult mice, it was found that embryonic tissue could not be used for this purpose.