To evaluate the diagnostic and prognostic significance of the N-terminal propeptide of collagen Type III (Col 1–3) in chronic liver disease, the peptide level was measured in the serum of 4 patients with primary biliary cirrhosis, 5 with chronic persistent hepatitis, 12 with chronic active hepatitis, and 1 with autoimmune hepatitis, for a period of 2 to 10 years and compared with liver function and histology. In primary biliary cirrhosis, Col 1–3 peptide levels were always elevated, regardless of medical therapy; however, after liver transplantation in one patient, the Col 1–3 peptide level decreased. In chronic persistent hepatitis, the peptide level fluctuated around the upper limit of normal. Among patients with chronic active hepatitis, the Col 1–3 peptide level normalized in 2 patients during remission, but was elevated in 7 patients who developed cirrhosis. Only in a patient with autoimmune hepatitis was the Col 1–3 peptide level normal, although the patient developed cirrhosis during prednisone therapy. When prednisone was withdrawn, the Col 1–3 peptide level increased. The data suggest that the serum Col 1–3 peptide may estimate the course of liver fibrosis in chronic liver disease and has prognostic value, particularly in chronic active hepatitis. Persistent elevation suggests ongoing fibrosis and development of cirrhosis; normalization suggests remission.