Sera from 64 patients with HBsAg-negative chronic liver disease with or without cirrhosis were investigated for aminoterminal peptide of type III procollagen (sP-III-P) as a suitable marker of hepatic fibrosis; 244 healthy control subjects were included in the study. A close correlation (p less than 0.01) between sP-III-P levels and histological activity was observed; on the contrary, no correlation was found between the same serum marker of liver fibroplasia and biochemical activity or clinical severity of the disease. We conclude that sP-III-P as a suitable marker of liver overload of collagen fibers is strongly correlated with the histological activity of the disease. Local immune reactions produce soluble substances that might stimulate fibroblastic activity. The test has a significant sensitivity and a very high specificity as a marker of chronic liver disease with histological activity.