Although numerous etiologies for endometriosis have been proposed, it is clear that retrograde menstruation and cell-mediated lymphocytotoxicity each play a significant role in the disease's development. A comprehensive theory of pathogenesis of endometriosis holds that development of the disorder depends upon amount of retrograde menstruation and the ability of the immune response to remove the debris. To test this theory, 64 women with mullerian anomalies and intra-abdominal surgery were evaluated for the presence or absence of endometriosis, patency of tubes, hematocolpos or hematometra, and outflow obstruction. Results demonstrated that endometriosis was present in ten of 13 women with functioning endometrium, patent tubes, and outflow obstruction, whereas it could be identified in only 16 of 43 women with no obstruction (77 versus 37%, P less than .01). Similarly, eight of nine women with hematocolpos or hematometra had endometriosis, while only 18 of 47 with functioning endometrium but no hematometra/hematocolpos had it (89 versus 38%, P less than .01). None of the eight women without endometrium had endometriosis. These data support the concept that an increase in retrograde menstruation will increase the likelihood of endometriosis.