Serum levels of c-erbB-2 protein were measured by an enzyme immunoassay in 64 patients with lung adenocarcinoma. Immunohistochemical staining was performed in 40 of these tumors. The mean serum concentration was 16.5±8.5 U/mL (range: 3.4 to 49.0) in patients with lung adenocarcinoma, whereas it was 14.0±3.7 U/mL (range: 6.9 to 20.9) in 15 controls (1 U/mL= 0.61 ng/mL). Elevated concentrations (≥22.0 U/mL, control mean+2 SD) were observed in 17/64 lung adenocarcinoma patients (26.6%), as compared with none of the control subjects (p<0.05). Patients with stage IIIB or T4 disease had increased serum levels. The serum concentration was decreased significantly by surgical tumor ablation. Tissue overexpression was obtained in 17/40 cases (42.5%), and serum levels in patients with tissue overexpression were higher than in patients without overexpression. Serum c-erbB-2 protein may be a useful indicator of tumor burden in patients with lung adenocarcinoma.