Serum samples obtained from 133 patients with gynecologic malignancies were assayed for two tumor-associated antigen markers: CA125, an ovarian marker, and lipid-associated sialic acid, a nonspecific marker. In the patient population, there were 77 papillary serous and 19 unspecified ovarian adenocarcinomas, and 24 miscellaneous ovarian carcinomas. Thirteen patients had nonovarian malignancies. Sixty-nine percent (74 of 108) of the patients with known disease had abnormal CA125 levels, whereas only 32% (20 of 63) had abnormal lipid-associated sialic acid levels. Changes in CA125 serum levels reflected the disease status of the patients for whom there were serial serum samples. Normal levels of CA125 corresponded to no evidence of disease in 100% (six of six) surgically evaluated patients and 75% (30 of 40) of clinically evaluated patients. Changes in CA125 levels from normal to abnormal corresponded to disease progression in 80% (12 of 15) of the patients. Decreases in CA125 levels from abnormal to normal corresponded to complete clinical response in 55% (11 of 20), and partial clinical response in 45% (nine of 20). No such correlations were available for lipid-associated sialic acid antigen levels. For tumors that express CA125 antigen, serum levels appear to be a good marker for the extent of malignant gynecologic disease. Levels of CA125 that rose from normal to abnormal were usually associated with recurrent disease.