Objective: To assay the cathepsin D level in endometriotic tissue, to study the difference to uterine endometrium and the correlation to localization. Design: Prospective consecutive study on endometriotic tissue and endometrium. Setting: University clinic. Patients: Thirty-five women undergoing laparotomy for clinical indications. Interventions: Samples of endometriotic tissue and uterine endometrium were obtained simultaneously from the same woman at laparotomy, fresh frozen, and assayed using an immunoradiometric method. Main Outcome Measure: The cathepsin D level in endometrium and endometriotic tissue expressed in pmol/mg DNA. Results: The cathepsin D level was significantly higher in endometriotic tissue than in endometrium both in follicular and luteal phase. The highest values in endometriotic tissue were found in luteal phase, in ovarian lesions, and in primary lesions. In endometrium, but not in endometriotic tissue, there was a positive correlation between cathepsin D level and serum E(2) level. Conclusion: The level of the proteolytic enzyme cathepsin D is significantly higher in endometriotic tissue than in endometrium, which might be of importance for implantation and the invasive growth of endometriotic tissue.