CA-125, a cell-surface antigen, was measured by a radioimmunoassay in the serum of 414 women to determine its potential usefulness in the diagnosis and management of endometriosis. In women with minimal, mild, moderate, and severe endometriosis, the mean levels (+/- standard deviation) were 13.6 +/- 6.8, 22.8 +/- 15.5, 27 +/- 17, and 50 +/- 28 U/ml, respectively, and were significantly higher than mean levels (7.8 +/- 4.1) in 46 women with a normal laparoscopic examination. Higher mean CA-125 values also were observed in acute pelvic inflammatory disease, unexplained fertility, and pregnancy and during menstruation. The mean CA-125 value in women with treated endometriosis and a negative second-look laparoscopy was significantly lower than in women with untreated endometriosis. With the use of the 95% upper limit of 16 U/ml, the test had a sensitivity of 53% and specificity of 93%. The frequencies of elevated levels in minimal, mild, moderate, and severe endometriosis were 27%, 68%, 73%, and 100%, respectively. Changes in the CA-125 levels correlated with the clinical course of endometriosis in 37 of 44 (84%) women (P less than 0.001). The determination of CA-125 levels may assist in the evaluation and treatment of women with endometriosis.