Transforming growth factor-alpha (TGF-alpha) is a potent mitogenic polypeptide. It is secreted by a variety of transformed cells and tumors, modifying tumor growth through autocrine or paracrine mechanism. In the present study, serum levels of TGF-alpha were determined by enzyme-linked immunosorbent assay (ELISA) in 27 normal females, 116 patients with benign ovarian tumors, and 42 patients with epithelial ovarian cancers (10 with stage I, 7 with stage II, 19 with stage III, and 6 with stage IV). The ELISA assay could detect a minimum level of serum TGF-alpha concentration at 10 pg/ml. Serum samples were obtained from normal females and from patients with benign or malignant ovarian tumors before initial surgery, The detectable rates were 11% (3/27) in normal females, 28% (32/116) in benign ovarian tumors, and 62% (26/42) in ovarian cancers. The detectable rates in serous and endometrioid ovarian cancers were 71 and 70%, respectively, which were higher than the rate of 33% in mucinous type. However, there was no obvious relationship between the detectability of serum TGF-alpha and the stages of ovarian cancers. The mean concentration of TGF-alpha in ovarian cancer was 159.8 pg/ml, which was significantly higher than 27.7 pg/ml in benign ovarian tumors (P < 0.001) as well as 15 pg/ml in normal females (P < 0.001). The mean concentrations of serum TGF-alpha in stages I to IV ovarian cancers were 133.5, 96.2, 194.8, and 178.3 pg/ml, respectively. The mean concentration of serum TGF-alpha in any two stages of ovarian cancers was not statistically different. In conclusion, measurement of serum TGF-alpha can be used as a supplementary tumor marker to differentiate a malignant ovarian tumor from a benign one. However, the concentration of serum TGF-alpha has no special relation with the stage of ovarian cancer itself. Because of the small number of stage I ovarian cancers with detectable TGF-alpha in the present investigation, it would probably not be feasible to differentiate a stage I ovarian cancer from a benign ovarian tumor based only on the level of TGF-alpha in serum. (C) 1997 Academic Press.