Current evidence suggests that peritoneal inflammatory cell hyperactivation may be the essential pathologic abnormality in patients with endometriosis-associated subfertility. In these experiments we utilized an animal model to evaluate the use of an immunomodulatory agent as an alternative treatment for endometriosis-associated subfertility. The right uterine horn of 12 golden hamsters was resected and 2 x 2 mm squares were explanted onto the left uterine mesentery. Controls included hamsters undergoing uterine horn resection without endometrial explantation (n = 6) and nonsurgically treated animals (n = 6). Ovulation induction was initiated 6 weeks postoperatively with 40 IU of pregnant mare's serum gonadotropin on day 1 and 40 IU of human chorionic gonadotropin on day 3. Groups of six explant-bearing hamsters and six nonsurgical control hamsters were treated with verapamil (250 micrograms/kg every 8 hours subcutaneously), a calcium channel-blocking agent known to inhibit macrophage activation, from day 1 to 48 hours after administration of human chorionic gonadotropin. Animals were then killed and the number of embryos and oocytes in left tube counted as a reflection of reproductive performance. Fertilization was completely inhibited in animals bearing uterine explants. Treatment with verapamil dramatically reversed this effect. These data suggest that periovulatory treatment with an immunomodulatory agent such as verapamil may be an effective alternative to conventional treatment for endometriosis-associated subfertility.