Tumor-associated glycoprotein (TAG-72) is an antigen detected by the monoclonal antibody B72.3 that is expressed by a wide variety of human malignancies and in normal secretory endometrium. Serum TAG-72 may be elevated in women with endometriosis, but the distribution of TAG-72 in this disorder has not been well studied. Accordingly, TAG-72 was assayed by immunohistochemical staining in 26 endometriotic implants collected at various times of the menstrual cycle and compared to that in 56 samples of normal endometrium, in 8 cases from the same patient. TAG-72 expression was markedly discordant between normal and ectopic endometrium. Unlike proliferative phase endometrial samples, which were uniformly negative, endometriotic implants were TAG-72 positive in 50% of the cases. Like normal endometrium, all except very early secretory phase endometriosis was positive. Based on our current understanding of TAG-72 expression, this unique estrogen-repressed glycoprotein may be a useful probe to study the basis for phenotypic alterations noted in endometriosis, some of which probably contribute to the infertility associated with this disease. Moreover, the presence of B72.3 in nonmalignant tissues puts in question it usefulness in screening for malignancies.