Offspring of pregnant rats treated with a high dose of aspirin on day 11 of gestation frequently had predominantly right-sided polydactyly of the hindlimbs at term. Aspirin-treated embryos removed on day 12 exhibited a unique pattern of preaxial mesodermal cell death in the hindlimb buds. In addition, these embryos had a delay of the normal episode of cells death in the preaxial apical ectodermal ridge and an absence of cell death in a zone of physiological necrosis in the preaxial mesoderm thought to be instrumental in controlling preaxial digit formation. The role of cell death in the pathogenesis of polydactyly is discussed.