Sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken') was developed to determine the levels of c-erbB-2 oncogene product (ErbB-2 protein) in human sera, and a clinical investigation was carried out to evaluate this novel oncogene product. The mean serum concentration of the ErbB-2 protein determined from 364 donors was 4.0 +/- 0.69 ng/ml (mean +/- SD) for females and 4.5 +/- 0.96 ng/ml for males. Cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positivities of serum ErbB-2 protein in patients with breast carcinoma were 13.0% for primary cases and 47.9% for recurrent cases. Patients with hepatic disorders also had positive serum ErbB-2 protein levels, ie, 43.8% (7/16) for hepatocellular carcinoma and 28.9% (11/38) for hepatitis and liver cirrhosis, although the increase was slight and barely exceeded 10 ng/ml. In comparison with the levels of other tumor markers, such as CEA, CA 15-3 and NCC-ST 439, the serum ErbB-2 level was shown to have poor correlations, and was thus assumed to be useful for combination with those tumor markers. In serial determinations of serum ErbB-2 protein in two patients with recurrent breast carcinoma, the antigen increased preceding the increases in the other tumor markers, thereby also showing usefulness as a monitoring marker for breast carcinoma. In conclusion, these results indicated that ErbB-2 measurement improves the assessment of breast cancer in combination with other tumor markers and is useful as a tool for monitoring the clinical condition and the response for treatment in breast cancer.