We evaluated histological activity index (HAI) score and serum markers of liver fibrosis, type IV collagen (IV-C) and prolyl hydroxylase (PH), to analyze whether they are predictors of response to interferon (IFN) treatment for chronic hepatitis C. Efficacy of IFN therapy was evaluated in 16 patients. Mean serum levels of IV-C and PH before treatment in five responders were lower than those in 11 non-responders (not significant). Among seven patients whose IV-C values were less than 200 ng/ml and PH less than 80 ng/ml, five patients (71.4%) were responders. The response rate of these seven patients was significantly (P < 0.005) higher than that (0%) in the other nine patients. When patients were histologically divided by the total HAI scores, the response rate to IFN in patients with low HAI score (10 or less) was 71.4% (five of seven patients), while that in patients with high HAI score (more than 10) was 0%. The result that the response rate to IFN in patients with low serum IV-C and PH levels equaled that in patients with low HAI score suggests that the efficacy of IFN treatment may be predictable by measuring serum levels of IV-C and PH in patients with chronic hepatitis C.