The effect of the cell death inhibitor Bcl-2 and its homologues on cell cycle regulation was explored in lymphocytes and cell lines. Expression of a bcl-2 transgene reduced proliferation of thymocytes and delayed cell cycle entry of mitogen-stimulated B and T lymphocytes. Overexpression of Bcl-2, Bcl-xL or adenovirus E1B19kD substantially delayed serum stimulation-induced S phase entry of quiescent NIH 3T3 fibroblasts. Bcl-2-mediated cell survival and growth inhibition are both antagonized by Bax. Bcl-2, Bcl-xL and E1B19kD, but not Bcl-2 mutants that are defective in blocking apoptosis, suppress growth of colon carcinoma cells. This evidence that regulation of cell survival is coupled to control of cell growth has implications for normal cell turnover and tumorigenesis.