Nine patients with chronic hepatitis C who responded with normal or near-normal serum alanine aminotransferase (s-ALT) levels during an initial interferon alpha-2b treatment course, but who had subsequent relapses with elevated s-ALT levels after treatment cessation, were retreated once (3 patients) or twice (6 patients). The liver histological findings before the first and after the last treatment course were compared. The mean follow-up time between the initial and the follow-up assessment was 44 months (range 34-53). The histological findings were classified as chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) or cirrhosis (Ci) by using a numerical scoring system assessing each portal zone separately. In the initial biopsy, 2 patients were classified as having CPH and 7 as having CAH, 2 of whom with signs of cirrhosis. According to the conventional classification, 4/9 (44%) patients improved after treatment, 3/9 (33%) remained unchanged, and 2/9 (22%) deteriorated. The mean histological scores for the necro-inflammatory parameters: portal inflammation, piecemeal necrosis, spotty necrosis and fibrosis improved, but the changes did not reach statistical significance. We conclude that repeated interferon alpha-2b treatment courses are probably beneficial in patients with chronic hepatitis C who show a non-sustained response to interferon, since studies on the natural course of chronic hepatitis C have indicated a progressive deterioration of the histological picture in many untreated patients, most marked among those with CAH.