We serially measured the levels of serum N-terminal peptide of type III procollagen (PIIINP), the 7S domain of type IV collagen (IV-7S), and hyaluronate (HA) before (0 month), at the end (6 months), and 24 weeks after the end of interferon therapy (12 months) in patients with chronic hepatitis type C to estimate the effects of interferon alfa (IFN-alpha) on serum levels of hepatic fibrogenesis markers. One hundred twenty-one patients with chronic hepatitis type C received intramuscular injection of 6 million U of natural IFN-alpha for 24 weeks. Patients were divided into three groups: sustained complete response (CR-S), complete response with rebound (CR-R), and nonresponse (NR). Serum PIIINP, IV-7S, and HA levels were significantly decreased and reached normal levels at 12 months in CR-S; only IV-7S levels were significantly decreased at 12 months in CR-R, whereas these levels remained abnormally high in the NR. These results suggest that IFN- alpha therapy could lower the levels of serum hepatic fibrogenesis markers along with improvements in hepatic inflammation.