The levels of ErbB-2 protein in serum samples from patients with breast cancer, other various malignant tumors, and benign diseases were determined using the sandwich EIA for clinical evaluation. In 364 healthy blood donors, cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positive rate of primary breast cancer was 13.0% (24/185) and that of recurrent breast cancer was 51.2% (62/121). No significant correlation was found between serum levels of ErbB-2 protein and other tumor markers, such as CEA, CA 15-3, and ST 439. Measurement of ErbB-2 protein in combination with these tumor markers showed increased sensitivities. The positive rates and levels of ErbB-2 protein in sera of patients with metastasis to multiple organs were significantly higher than those in patients with metastasis to only a single organ. In postoperative follow-up of two patients with recurrent breast cancer, the levels of ErbB-2 exceeded its cut-off value a few months earlier than did the other tumor markers. These results indicate that the measurement of the ErbB-2 protein in serum is useful for the diagnosis and a monitoring the relapse of breast carcinoma.