Apoptosis in corpus luteum (CL) is induced by prolactin (PRL) in female rats. PRL-induced apoptosis in CL is mediated by the Fas/Fas ligand (FasL) system. The CL consists of steroidogenic and non-steroidogenic cells, including immunocytes. Fas mRNA was detected only in the luteal steroidogenic cells, and FasL mRNA was expressed only by the non-steroidogenic CD3-positive luteal immunocytes. Removing the luteal immune cells from the luteal cells inhibited PRL-induced luteal cell apoptosis effectively. Thus, FasL-expressing non-steroidogenic luteal immunocytes are required for PRL-induced luteal cell apoptosis and heterogeneous induction of apoptosis by Fas/FasL in CL.