An intraperitoneal inflammatory exudate has been repeatedly observed in infertile women without mechanical compromise of the pelvic viscera, particularly with endometriosis. This is manifested by increases in the peritoneal fluid volume, leukocyte number, and proteolytic enzyme concentrations. We tested the hypothesis that the stimulus responsible for eliciting this intraperitoneal inflammation is retrograde menstruation by measuring the peritoneal fluid volume and leukocyte count in 16 infertile women with endometriosis before and after ovulation suppression with medroxyprogesterone acetate, 30 mg/day for 4 months. Medroxyprogesterone acetate therapy significantly reduced the peritoneal fluid volume (22.5 +/- 4.1 versus 6.8 +/- 0.9 ml mean +/- SE, p less than 0.0001), the peritoneal fluid leukocyte count (30.7 +/- 6.5 versus 7.1 +/- 0.7 x 10(6) cells per patient, p less than 0.0001), and American Fertility Society score (23.2 +/- 5.1 versus 15.4 +/- 4.1, p less than 0.0002). We conclude that medroxyprogesterone acetate treatment reduces the intraperitoneal exudate associated with endometriosis. These results support the contention that the stimulus eliciting the intraperitoneal inflammation in infertile women with endometriosis is retrograde menstruation.