In 504 patients with chronic hepatitis C who underwent liver biopsy, the correlation between serum ALT levels and histologic liver inflammation was investigated, and the effects of age, sex, and degree of histologic liver fibrosis on this correlation were analyzed. Serum ALT levels were significantly higher in male than in female patients only when activity of hepatitis was mild. In contrast, ALT levels were significantly higher in younger (< or = 50 years old) than in older patients only when activity of liver inflammation was severe. Fibrosis was closely associated with activity of hepatitis and, also, serum ALT level. More importantly, a significant number of older patients and patients with severe hepatic fibrosis had severe hepatic inflammation even when their serum ALT level was not markedly elevated (< or = 70 IU/L). Age, sex, and degree of liver fibrosis independently influenced serum ALT levels in patients with chronic hepatitis C.