Somatic mouse cells hybrids formed by fusion of nontumorigenic 3T3 closely related SV40-transformed SVT2 cells were analyzed in a study designed to probe the genetic basis of the multiple phenotypic changes induced by SV40 transformation. These hybrids showed noncoordinate expression of the transformation phenotype. Although they cloned at high efficiency in medium with low serum and expressed the SV40 T-antigen of the SVT2 parent, hybrid cells grew poorly without anchorage and exhibited a cell and colony morphology intermediate between that of the parents. Tumorigenicity was assayed quantitatively by subcutaneous coinjection into athymic nude mice of serial dilutions of 10(2) to 10(5) hybrid cells with 10(7) lethally irradiated 3T3 cells. The results showed that 100--1000 times more hybrid cells had to be injected for tumor formation than were required with SVT2. These and other observations show that most 3T3/SVT2 hybrid cells are not tumorigenic but that each population contains a rare subset of tumorigenic cells.