Somatic cell hybrids between SV40-transformed human fibroblast cells and normal human fibroblasts were isolated and tested for growth in vitro and in athymic nu/nu (nude) mice. All hybrid cells formed by a cross of WI-18/VA-2, a tumorigenic SV40-transformed human fibroblast, with IMR-90 expressed T antigen and grew in the appropriate selective medium. However, tumorigenic potential ranged from completely suppressed to fully expressed in these hybrid cells. In addition, all hybrid cells formed between LNSV, a nontumorigenic SV40-transformed human fibroblast, and IMR-90 were nontumorigenic. Previous studies have shown that the tumorigenic potential of hybrids cells formed between a variety of human tumor cell lines and normal human fibroblasts is completely suppressed. These results imply that the genetic control of tumorigenic expression in virally transformed human cells differs from that seen in spontaneously arising human tumor cells.