The ovarian histopathology of bitches immunized with crude (cPZP) or partially purified (pPZP) porcine zona pellucida proteins was examined in order to determine the cause of abnormal estrous cycles. The majority of immunized bitches had ovarian cytes. Those immunized with cPZP had follicular cysts lined with a thin layer of granulosa cells, while in those immunized with pPZP, the cysts were lined by a basement membrane with a clump of luteinized cells. In two bitches immunized with cPZP, oocytes were present only in primordial follicles. Similar abnormalities were not found in a bitch immunized with human serum albumin or in 12 untreated bitches. Oocytes flushed from the oviducts of mated, immunized bitches were degenerating, which may have been a primary cause of infertility in such bitches. Ovaries studied 2-6 weeks after immunization showed no loss of gap junctional communication between oocytes and granulosa cells, nor was any inflammatory reaction seen. IgG was bound to the zona as revealed by fluoresceinated protein A staining of frozen sections of those ovaries. Abnormal estrous cycles in PZP-immunized bitches appear to result from follicular dysgenesis or cyst formation, but the etiology of these conditions is unresolved.