BACKGROUNDThe serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin‐2 receptor alpha (sIL‐2Rα) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms.METHODSCA125, TPS, and sIL‐2Rα concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms.RESULTSCA125, TPS, and sIL‐2Rα levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III–IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I–II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL‐2Rα). Concurrent measurement of CA125 and sIL‐2Rα in sera identified 100% of ovarian carcinomas in FIGO Stage I–II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL‐2Rα was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III–IV disease compared with patients who had FIGO Stage I–II disease (P = 0.002), whereas such correlations were not found for TPS or sIL‐2Rα. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL‐2Rα levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL‐2Rα levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms.CONCLUSIONSIn patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL‐2Rα values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL‐2Rα levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers. Cancer 2002;95:1886–93. © 2002 American Cancer Society.DOI 10.1002/cncr.10917