Serum type-III procollagen aminopropeptide (PIIIP) has been considered a marker of hepatic fibrogenesis. In an attempt to evaluate the clinical significance of serum PIIIP in patients with hepatitis B virus (HBV)-related liver diseases, the levels of the peptide were measured in 66 healthy adults and 200 patients with HBV-related liver diseases. As compared with the healthy adults (12.3 +/- 3.1 ng/ml), the serum PIIIP levels were significantly elevated in patients with acute hepatitis (17.4 +/- 6.6 ng/ml), chronic persistent hepatitis (18.3 +/- 4.9 ng/ml), and inactive liver cirrhosis (22.1 +/- 7.1 ng/ml). The PIIIP levels in patients with chronic active hepatitis (CAH) (33.9 +/- 23.1 ng/ml) were the highest among HBV-related liver diseases and had a tendency to increase with the severity of CAH. Of the liver-diseased patients with serum PIIIP levels greater than 30 ng/ml, 91% had a recent episode of severe hepatocellular damage, whereas 56% of patients with greatly elevated serum liver aminotransferase levels had no associated high increase in serum PIIIP levels. Thus, we suggest that fibrogenesis in HBV-related liver diseases is initiated by severe hepatocellular damage, but liver damage can also take place without prominent hepatic fibrogenesis. Serum PIIIP may be a serum marker to predict the active fibrogenesis of HBV-related liver diseases.