Apoptosis has been found to occur during regression of the corpus luteum (CL) in many species. The Pas (APO-1/CD95) receptor, a transmembrane protein that induces apoptosis in the cell when bound to Fas ligand (FasL), may be involved. This study established and quantitated the presence and regulation of Pas receptor and Fast in the rat Ct. during pregnancy and postpartum. Using immunohistochemistry, Fast was localized in Ct. during pregnancy and postpartum. Fas was localized at Day 1 of pregnancy and at the time of luteolysis. Both Fas and Fast mRNA were found to be expressed throughout pregnancy and postpartum using reverse transcription-polymerase chain reaction (RT-PCR). Relative quantitative RT-PCR established that expression of Fast mRNA increased significantly at Day 22 of pregnancy and decreased by Day 3 postpartum. Spontaneous apoptosis of raf: Ct. placed in an in vitro culture model with serum-free medium was examined by analysis of extracted DNA using 3' end-labeling. Treatment with an anti-rat Fas monoclonal antibody demonstrated a reduction in the occurrence of spontaneous apoptosis. These data support a role for Pas receptor and Fast in rat CL apoptosis during luteolysis.