To evaluate the diagnostic significance of the collagen Type III (Col 1–3) JV-terminal propeptide of procollagen Type III, with respect to activity and degree of liver fibrosis, Col 1–3 serum concentrations were measured in 111 patients with chronic liver diseases and in 60 patients were correlated with liver histology and morphometry. Col 1–3 was measured by a specific radioimmunoassay. Biopsies were read without knowledge of diagnosis. Periportal and intralobular lesions were assessed semiquantitatively by allocating 1 of 4 severity grades to each parameter. All portal areas were measured morphometrically. Compared to 27 normal controls, Col 1–3 concentrations were significantly elevated in patients with untreated chronic active hepatitis, cirrhosis and primary biliary cirrhosis, but not in chronic persistent hepatitis or fatty liver. Morphometrically measured portal tract area significantly correlated with Col 1–3 plasma levels. Among the semiquantitatively measured periportal lesions, the number of fibroblasts exhibited the closest relationship with Col 1–3 levels; there was no relationship between Col 1–3 levels and intralobular lesions. These data suggest that Col 1–3 serum levels reliably reflect the activity and degree of liver fibrosis and are useful along with liver biopsy in follow-up of patients with chronic liver disease.