Patients with chronic hepatitis C virus (HCV) infection develop various extrahepatic complications. In this study, we analyzed as following. (1) The prevalence and interrelation of multiple extrahepatic manifestations. (2) Exact factors that are related to multiple extrahepatic manifestations. Consecutive autopsies of 261 cases with HCV infection that had undergone autopsy in 1988-1998 were enrolled. One hundred and forty consecutive patients who had gastro enteric carcinoma and underwent autopsy after death in our institution during the same period were used as controls. These 140 patients did not have hepatitis virus and chronic hepatitis or liver cirrhosis histologically. The prevalence of glomerulonephritis (GN), sialadenitis, thyroiditis, and idiopathic pulmonary fibrosis (IPF) was determined histologically. 'Multiple extrahepatic complications' was defined as the presence of two or more of the above four extrahepatic complications. Multiple logistic regression analyses of the risk for the multiple extrahepatic manifestations were performed. GN was present in 58.6% (153 cases), sialadenitis in 16.1% (42 cases), thyroiditis in 7.7% (20 cases), and IPF in 5% (13 cases) in cases of HCV infection. In addition, 37 out of 261 (14.2%) and seven (2.7%) cases had two and three extrahepatic complications, respectively. Multivariate analysis showed that multiple extrahepatic complications correlated with high serum gamma-globulin levels (>/=2.5 g/dl) and high serum total bilirubin levels (>/=1.2 mg/dl) about 1 year before death. Moreover, about 70-80% of patients with sialadenitis, IPF, or thyroiditis had other extrahepatic manifestations. HCV-positive patients with high serum gamma-globulin or high total bilirubin are at high risk of multiple extrahepatic complications.