BACKGROUND: The HER-2 neu (c-erbB-2) oncogene product p185neu is expressed by most ovarian cancers and overexpressed in approximately 30%. METHODS: Sera from patients with ovarian cancer were evaluated for neu antigen using an enzyme-linked immunoassay and for CA 125 antigen by radioimmunoassay. Tissue levels of neu from the same patients were determined by immunohistochemical staining with anti-neu monoclonal antibody. RESULTS: Elevated levels (> 2050 human neu unit [HNU]/ml) of circulating neu determinants have been detected in sera from 15% of 48 patients. Of 45 patients for whom tumor tissue had been cryopreserved, overexpression of neu was found in 17 by immunohistochemical analysis; of these 17, serum neu levels were elevated in 5 (29%). Among the 28 patients with normal to moderate tissue expression of neu, only 2 (7%) had elevated serum neu levels. Thus, elevated serum neu levels predicted tissue overexpression with a specificity of 93%. Serum neu levels were not related to serum levels of CA 125. CONCLUSION: Serum and tissue levels of neu correlate in patients with epithelial ovarian cancer.