Plasma vitronectin concentration was measured in 60 patients with chronic hepatitis C before and after interferon alpha treatment. The plasma pretreatment levels of vitronectin in the interferon non-responders was significantly lower than those in the interferon sustained and transient responders, but the levels were not different in the latter two groups. After interferon therapy, the plasma levels of vitronectin were significantly increased in all three groups, and they were correlated with the albumin levels. Absolute changes of plasma vitronectin before and after interferon treatment were significantly related to initial levels, but they were not related to those of albumin or alanine aminotransferase levels. The values of sensitivity and specificity for plasma vitronectin in the sustained responder and non-responder were 45% and 95% for each. These results suggest that chronic hepatitis C patients with low levels of plasma vitronectin may have a weak response in interferon therapy.