Apoptosis is an active cell 'suicide' essential for the elimination of superfluous cells during diverse physiological processes in essentially all animal species. Although regulation of apoptosis by extracellular mediators is cell type-specific, new insights based on characterization of conserved intracellular effectors have suggested that intracellular pathways leading to apoptosis in diverse organisms is regulated by a group of evolutionarily conserved genes including ced-9/Bcl-2, ced-4/Apaf-1 and ced3/caspases gene families. To study whether the Bcl-2 family proteins are important in the regulation of ovarian cell apoptosis, we have used transgenic mice and yeast 2-hybrid protein protein interaction assay to characterize the roles of Bcl-2 family proteins in ovarian atresia. The use of 2-hybrid analysis resulted in the isolation of a novel pro-apoptotic Bcl-2 protein, Bcl-2-related ovarian killer (Bok) and the identification of upstream mediators for ovarian cell apoptosis.