The Fas antigen (Fas) is a cell-surface receptor protein that mediates apoptosis-inducing signals and plays an important role in the immune system. Significant amounts of Fas mRNA can be detected not only in lymphoid organs but also in the liver, heart, and ovary. In the ovary, apoptosis is thought to cause follicular atresia and luteolysis. We have investigated the involvement of Fas in these events. Here we report that Fas protein is expressed on granulosa and luteal cells but not on oocytes in the ovary. An injection of anti-fas monoclonal antibody with apoptosis-inducing activity into adult mice enhanced follicular atresia and luteolysis. After the injection, the corpora lutea disappeared and the number of follicles containing pyknotic granulosa cells increased. There were also fewer ovulated ova and lower levels of luteal cell-produced progesterone. Furthermore, as the result of a non-functional Fas/Fas ligand system, mature ovaries from the mouse mutant lpr (lymphopuoliferation) were histologically abnormal in terms of follicular development, in that the number of secondary follicles significantly increased. These results suggested that Fas plays an important role in follicular atresia and luteolysis in the ovarian physiology of adult mice. (C) 1997 Wiley-Liss, Inc.