Objective: In previous studies we found that patients with endometriosis (EDT) have a significant enhancement of cell proliferation and diminished apoptosis of eutopic endometrium, and both factors may contribute to its etiopathogenesis. The purpose of this study was to assess the effect of combination oral contraceptives (COC) treatment on proliferation, apoptosis and its regulation by the expression of Bcl-2 and BAX, of eutopic endometrial tissue from patients with EDT and control women (C). Design: Linear study (non-randomized) by endometrial biopsies of patients undergoing gynecologic surgery and voluntary consenting controls. Materials/Methods: 11 EDT patients and 9 C had an endometrial biopsy before and after (11 EDT and 3 C) 30 days of COC. The assessment of cell proliferation was done by the presence of nuclear protein Ki-67 before and after COC. In the same biopsies apoptosis were detected by TUNEL assay; and its regulation, by the expressions of Bcl-2 and Bax, assessed by using immunohistochemical techniques (Meresman et al. Fertil Steril 2000;74:760–6). Proliferation was measured as the percentage of Ki-67 positive cells and the other parameters were quantified as the number of positive cells/field at 630x magnification. Results: Before COC, EDT patients had an increased cell proliferation at the epithelial (EP) and stromal (ST) fractions compared to C (EP: p < 7.9 10−5, ST: p < 7.4 10−6). Simultaneously, a significantly decreased apoptosis, assessed by TUNEL, in EP (p < 0.002) and in ST (p < 0.0007), was observed in these patients correlating with an increased Bcl-2 and decreased BAX expression. After COC we found that, in EDT, patients cell proliferation was significantly decreased both in EP (p < 0.0002) as in ST (p < 7.2 10−5) however in this last fraction proliferation remains augmented with respect to C before COC (p < 0.02). At the same time, apoptosis of EP and ST was significantly augmented (p < 0.018 and p < 0.02 respectively vs. EDT before COC) and particularly in ST was similar to C before treatment (N.S.). Concurrently, after COC, EDT patients showed a significant increase in BAX expression and a decrease in Bcl-2 expression. At the same time in C, after COC, there was a significant increase in ST apoptosis (p <0.05), however no significant changes in cell proliferation was observed. Conclusions: According with our results COC significantly diminished cell proliferation, induced apoptosis and an increased expression of BAX in eutopic endometrial tissue from EDT patients. This data may have clinical relevance in the etiopathogenesis and treatment of endometriosis