Objective: To identify factors influencing the development of endometrial autografts in a monkey model of endometriosis. Design: Prospective, comparative study. Setting: Animal research unit. Subjects: Thirty regularly cycling cynomolgus monkeys in three groups of 10 each. Interventions: Endometrium was minced and spilled into the cul-de-sac in group 1, In group 2, the tissue additionally was digested enzymatically. In group 3, the tissue was incubated with a protease inhibitor. Main Outcome Measures: Staging laparotomies after 3 weeks and 3 months. Results: In groups 1, 2, and 3, moderate or severe disease was seen in eight, two, and four monkeys, respectively, after 3 weeks and in eight, three, and two monkeys, respectively, at 3 months. Conclusion: An intact structure leads to ectopic implantation of endometrial Fragments in most cases. Conversely, enzymatic digestion of endometrial fragments and treatment with proteinase inhibitor impair ectopic growth. Intrinsic endometrial factors that influence extracellular matrix remodeling may play a role in the pathogenesis of human endometriosis.