To elucidate the clinicopathological course and the role of hepatitis C virus in posttransfusion and sporadic chronic non-A, non-B hepatitis in Taiwan, we retrospectively studied 85 histologically confirmed patients with long-term follow up. Antibodies against hepatitis C virus (anti-HCV) by a second-generation assay were positive in 81% of the patients: 88% in the posttransfusion group and 76% in the sporadic group. Clinical manifestations were generally mild, and were noted in only half of the patients. During follow up, 33% (28 of 85 patients) had episodes of acute exacerbation of chronic liver disease and 24% (20 of 85) had normalized liver tests. Patients with normalized liver tests were usually anti-HCV negative (55% vs. 8%, p < 0.001). In 34 patients who had had blood transfusions, initial liver biopsies revealed chronic active hepatitis in 41%, active cirrhosis in 6%, and inactive cirrhosis in 9%. Follow-up biopsies in eight patients in this group showed histological progression in three after an average of 40.6 months. In the 51 sporadically infected patients, initial work-up revealed chronic active hepatitis in 37%, active cirrhosis in 4%, and inactive cirrhosis in 14%. Among the nine who underwent repeated biopsies, only one (11%) had progression. Patients above age 40 displayed more severe histologic activity than those below 40 (p < 0.005). Three patients, all with cirrhosis, died of hepatocellular carcinoma 7 to 12 years after follow up. Further genotyping study of hepatitis C virus in 28 patients showed that type II virus was most predominant in Taiwan and histologic severity was similar among patients infected with different genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)