OBJECTIVE: We investigated the correlation between serum complement component 3 (C3) levels and metabolic and histological abnormalities in patients with chronic hepatitis C (CH-C). METHODS: Obesity and insulin resistance were estimated by calculating body mass index (BMI) and the values of the homeostasis model for assessment of insulin resistance (HOMA-IR), respectively. Severity of hepatic steatosis and fibrosis were evaluated by New Inuyama Classification and the classification proposed by Brunt and colleagues, respectively. The degree of hepatic C3 expression was examined, using an immunohistochemical procedure. RESULTS: Serum C3 levels were significantly correlated with BMI, HOMA-IR value, and serum triglyceride levels in CH-C patients. Histological analysis revealed that serum C3 levels were significantly elevated in proportion to the severity of hepatic steatosis in such patients. The serum C3 level tended to increase as the severity of hepatic fibrosis progressed. However, the degree of C3 expression in hepatocytes was not associated with serum C3 level among those patients. CONCLUSIONS: These results suggest that the elevation of serum C3 levels may reflect obesity, insulin resistance, and/or hepatic steatosis in patients with CH-C, and that the increase in the synthesis of C3 may derive from the activation of cells other than hepatocytes in those patients.