In a series of studies to more precisely localize the cellular sites of expression of the cyclin-dependent kinase (Cdk) family members in reproductive organs, we observed a striking expression of Cdk5 in atretic follicles in the ovary, particularly in granulosa cells that appeared to be dying. We determined that these granulosa cells were undergoing apoptotic cell death using the in situ DNA fragmentation assay. To extend the generality of the association of Cdk5 with apoptotic cells, we examined its expression as it correlated with the detection of apoptosis in a number of developmental paradigms, including regions of the embryonic nervous system, the developing eye, and the developing limb. Finally, the association of apoptosis and Cdk5 expression and associated kinase activity was examined in the limb and in an induced cell death system, that of androgen withdrawal-induced regression of the prostate gland in male mice. These observations provide new insight into the possible function of this novel Cdk during both differentiation and apoptotic cell death.