Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) recently have been shown to play a physiological role in the female genital system, including the ovarian follicular system. However, little is known about the role of the IGF system in malignant ovarian disease. To assess possible mutual correlations between alterations in circulating IGFBP profiles and tumuor markers in patients with epithelial ovarian cancer, we performed an RIA for IGFBP-2 and IGFBP-3 and a Western ligand blotting (WLB) in serum samples from 20 patients with epithelial ovarian cancer, 10 patients with benign ovarian tumors, and 8 healthy age-matched controls. The epithelial ovarian cancer group had a mean IGFBP-2 level that was 253% (RIA) and 105% (WLB) above that of controls. IGFBP-2 even correlated positively with the highly sensitive serum tumor marker, cancer antigen 125 (CA 125) (r = 0.71, P < 0.001) but not with the less sensitive tumor-associated trypsin inhibitor. In contrast, serum IGFBP-3 (by RIA and WLB) was decreased in patients with ovarian cancer, and IGFBP-3 proteolytic activity was detectable in some of the patients. Neither IGFBP-3 nor IGFBP-3 proteolytic activity correlated with CA 125; but the former correlated inversely, and the latter positively, with tumor-associated trypsin inhibitor. In conclusion, IGFBP-2 levels are high in serum of epithelial ovarian cancer patients, and the increment in serum IGFBP-2 correlates positively with CA 125. Alterations in serum IGFBP-2 levels may therefore, serve as a potential additional marker for ovarian cancer.