To evaluate the diagnostic significance of the amino-terminal propeptide of procollagen type III (P-III-P) in monitoring chronic liver disease, serum P-III-P concentrations were measured in 46 patients with severe chronic active hepatitis (CAH) at entry and at remission during a therapeutic clinical trial. Coded sera were analyzed for P-III-P concentrations by both a standard radioimmunoassay and a recently developed and potentially more precise radioimmunoassay that uses Fab fragments rather than intact antibodies for binding antigen. As compared with conditions in 22 normal controls, P-III-P concentrations were elevated in 98% and 72% of patients with CAH by use of the standard and Fab radioimmunoassays, respectively. With treatment, P-III-P levels fell at remission to levels that were not significantly different from control values, as measured by both assays. The Fab radioimmunoassay, either alone or combined with the standard radioimmunoassay, provided no advantage over the standard radioimmunoassay alone. Serum P-III-P levels, as measured by either assay, correlated poorly or not at all with standard liver function tests and with histologic grade of disease. These data suggest that P-III-P serum levels are abnormal in severe CAH but normalize when remission of disease has been achieved. Consequently, serum P-III-P levels may be a diagnostic aid in the sequential evaluation of patients with severe CAH requiring treatment, and this test deserves further investigation. In this regard, the standard P-III-P assay has greater diagnostic accuracy than the Fab assay.(ABSTRACT TRUNCATED AT 250 WORDS)