BACKGROUND. Ovarian cancer is the fifth most common cause of cancer-related death in American women. The median age at diagnosis is about 62 years; incidence rises rapidly after age 60. Pelvic examination has been the primary method for detection of ovarian carcinoma. It is insensitive for the detection of early disease, however: most women present with disease beyond the pelvis (Stages III and IV) and are not curable with existing techniques. Two new technologies may be useful as screening tools for earlier detection of ovarian cancer. CA 125 is an antigenic determinant expressed on an ovarian cancer cell line. Transvaginal ultrasound (TVUS) images the ovaries from within the vagina and can be performed by a technician in about 10 minutes. In small preoperative studies of women with ovarian masses, serum CA 125 levels have been elevated (typically above 35 U/ml) in over two-thirds of cases and in up to 50% of Stage I cases. The test is not absolutely specific: elevations have been reported with pregnancy, endometriosis, menstruation, benign ovarian tumors, and with cancers of the breast, colon, pancreas, lung, stomach, and liver. Nevertheless, the specificity of CA 125 in postmenopausal women has been reported at about 95% or more. TVUS provides higher resolving power for ovarian abnormalities than transabdominal ultrasound or physical examination; however, experience with it is limited. CA 125 and TVUS may be complementary. CONCLUSIONS. For these reasons, the National Cancer Institute is planning a randomized trial of all three tests versus routine medical care in women of ages 60-74 years. This is part of a larger trial to determine the efficacy of screening for lung, colorectal, and ovarian cancers in women, and for lung, colorectal, and prostatic cancers in men. Seventy-four thousand women will be randomized in the study.