Preoperative sera were assayed for tumor-associated antigens CA 125, TAG 72, and CA 15-3 in 100 women with pelvic masses. Serum CA 125 levels were elevated above 65 U/mL in 83% of 42 patients with ovarian malignancies, in 58% of 12 patients with nonovarian malignancies, and in 17% of 46 patients with benign pelvic masses. Elevations of TAG 72 and CA 15-3 levels occurred less frequently in all groups of patients. Serum CA 125 levels distinguished most effectively between patients with malignant pelvic masses and those with benign pelvic masses, having a sensitivity of 78% and a specificity of 83% at a threshold level of 65 U/mL. When comparing 33 patients with epithelial ovarian carcinomas to 46 patients with benign masses, the CA 125 level alone yielded a sensitivity of 88% with a specificity of 83%. Coordinate elevations of CA 125 (above 65 U/mL) and TAG 72 (above 10 U/mL) or CA 15-3 (above 30 U/mL) distinguished ovarian epithelial carcinomas from benign masses with a sensitivity of 73% and a specificity of 98%, which improved to 81 and 100%, respectively, among patients over 50 years of age. Given the marked increase in specificity observed with this panel of three serum tumor-associated antigens, use of multiple markers might facilitate screening for ovarian carcinoma and appropriate referral of patients with pelvic masses for cytoreductive operations.