Objective: To investigate the effects of oxygen on the proliferation and angiogenesis of endometriosis in vivo. Design: Animal studies. Setting: Animal research facility. Animal(s): Thirty-six female severe combined immunodeficiency (SCID) mice, implanted with eutopic endometrium from seven endometriosis patients. Intervention(s): Human eutopic endometrial tissues were randomized to normoxia, hyperoxia, or hypoxia pretreatment and were subcutaneously implanted into estrogen-treated ovariectomized SCID mice. Main Outcome Measure(s): The growth and quality of the implants were measured, and the expression of proliferation-and angiogenesis-associated markers (i.e., Ki67, CD31, vascular endothelial growth factor, and hypoxia-inducible factor-1 alpha) were assessed using immunohistochemistry and Western blot analyses. Result(s): The growth curves of the implants were distinct with different oxygen pretreatments. The growth of the implants of the hypoxia group was significantly increased compared with the normoxia group, but the growth of the implants of the hyperoxia group was significantly decreased compared with the normoxia group. Microscopic examination indicated that lesions with hyperplastic cylindrical glandular epithelium were surrounded by the endometrial stroma in the hypoxia group, but the glandular epithelium was partially depauperate in the hyperoxia group. The expression of Ki67, CD31, vascular endothelial growth factor, and hypoxia-inducible factor-1 alpha in the hypoxia-pretreated implants was significantly higher compared with the hyperoxia or normoxia groups. Conclusion(s): Oxygen can alter the growth patterns of endometriosis implants in a SCID mouse model. Hypoxia pretreatment promoted the proliferation and angiogenesis of endometriosis, whereas hyperoxia pretreatment exhibited the opposite effect. (C) 2014 by American Society for Reproductive Medicine.