Problem: The aim of this study was to investigate the humoral immune response to the female reproductive tissues associated with endometriosis (grades I-III) (n = 52), compared with a group of healthy fertile women (n = 6). Method of study: An ELISA with cultured endometrial cell lines in monolayer was used to determine the presence of anti-endometrial antibodies (AEA). For anti-zona pellucida antibodies (AZPA) assessment a conventional ELISA was employed. The presence of antibodies to human sperm (ASA) was performed by the tray agglutination test (TAT). Results: Endometriosis grade III was associated with AEA in serum in the 45.4% of patients. The presence of AEA in serum is correlated to endometriosis severity. The 8.7% of women with endometriosis showed ASA, and the 10.9% of them were positive for AZPA. Antibodies specific for endometrial cells do not show reaction to any gamete antigen (sperm or oocyte), suggesting that they are not cross reactive. Conclusions: Severity of endometriosis is correlated with high titers of AEA.