The Bcl‐2 family of proteins regulate apoptosis, some antagonizing cell death and others facilitating it. It has recently been demonstrated that Bcl‐2 not only inhibits apoptosis but also restrains cell cycle entry. We show here that these two functions can be genetically dissociated. Mutation of a tyrosine residue within the conserved N‐terminal BH4 region had no effect on the ability of Bcl‐2 or its closest homologs to enhance cell survival and did not prevent heterodimerization with death‐enhancing family members Bax, Bak, Bad and Bik. Neither did this mutation override the growth‐inhibitory effect of p53. However, on stimulation with cytokine or serum, starved quiescent cells expressing the mutant proteins re‐entered the cell cycle much faster than those expressing comparable levels of wild‐type proteins. When wild‐type and Y28 mutant Bcl‐2 were co‐expressed, the mutant was dominant. Although R‐Ras p23 has been reported to bind to Bcl‐2, no interaction was detectable in transfected cells and R‐Ras p23 did not interfere with the ability of Bcl‐2 to inhibit apoptosis or cell cycle entry. These observations provide evidence that the anti‐apoptotic function of Bcl‐2 is mechanistically distinct from its inhibitory influence on cell cycle entry.