Mutations in the p53 gene are associated with a wide variety of human tumors, including those of the breast. To assess functionally the role of the p53 gene in the development of human breast cancer, we introduced either wild-type or mutant p53 cDNA into three human breast cancer cell lines by DNA transfection. The cell lines MDA-MB 468 and T47 D contain only single mutated copies of the p53 gene, whereas the status of p53 in the breast cancer cell line MCF 7 remains equivocal. Following transfection, MCF 7 cells continued to grow unaffected both in vitro and in vivo in the presence of high levels of expression of the exogenous wild-type p53 gene. In contrast, however, the continued expression of an exogenous wild-type p53 gene was incompatible with cellular growth in both the MDA-MB 468 and T47 D cell lines. Elevated levels of expression of the exogenous mutant p53 gene did not alter the growth of the cell lines in vitro. These data strongly suggest that the wild-type p53 gene can function as a suppressor of cellular growth in breast cancer cells. That the wild-type p53 gene does not suppress the growth of MCF 7 cells indicates that at least some human breast tumors can arise without functional inactivation of the p53 gene by mutation. These tumors may represent a separate prognostic group.