Serum type IV collagen fragment (7S collagen domain) was measured in 30 controls and 152 liver disease patients with a radioimmunoassay using a polyclonal antibody to human placenta 7S collagen. The serum concentrations of 7S collagen (mean +/- SD) were 4.2 +/- 0.9 ng/mL in controls, 5.1 +/- 2.0 ng/mL in acute hepatitis, 6.5 +/- 2.5 ng/mL in chronic inactive hepatitis, 9.5 +/- 3.8 ng/mL in chronic active hepatitis, 14.4 +/- 7.5 ng/mL in liver cirrhosis, and 14.4 +/- 6.9 ng/mL in hepatocellular carcinoma. In acute hepatitis, 7S collagen was slightly increased, whereas type III procollagen N-peptide and prolyl hydroxylase were markedly increased. In chronic liver disease, 7S collagen concentrations increased with the severity of the disease, and also reflected the degree of fibrosis. The serum 7S collagen concentrations were significantly correlated with those of type III procollagen N-peptide and prolyl hydroxylase in all subjects. These results suggest that serum 7S collagen concentration is a useful diagnostic aid for determining hepatic collagen metabolism in liver diseases.