Cancer antigen 125 (CA 125) is common to most epithelial ovarian tumors. Therefore, it is potentially a good marker of this disease. This hypothesis was evaluated by measuring the serum levels of CA 125 in 81 patients with ovarian cancer (25 with nonactive and 56 with active disease), in 105 patients of both sexes with nonovarian tumors, and in 171 healthy controls of both sexes. The serum levels of three other markers, tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin, beta subunit (beta-hCG), were also measured in the same 357 subjects. The results of this study clearly indicate the clinical irrelevance of both CEA and beta-hCG as tumor markers in ovarian carcinomas. Conversely, the clinical usefulness of CA 125 and TPA was confirmed. In particular, CA 125 and TPA showed comparable sensitivity, while CA 125 showed a higher specificity for ovarian cancer than TPA. The association of CA 125 with TPA was very useful in continuous observation of patients with active disease in order to evaluate the clinical effectiveness of the therapy. Moreover, for patients in clinical remission, the markers allowed early detection of a recurrence of the disease.