We sought to ascertain whether response to alpha interferon treatment could be predicted among patients with chronic active hepatitis C, and whether antipyrine clearance estimations would determine changes in liver function with this disease. The patients came from a randomized controlled trial, with patients who were initially untreated eventually being offered interferon treatment. Among 28 patients treated with interferon 18 (64%) responded with normalization of serum aminotransferase levels. Responders were less likely to have acquired hepatitis C by blood transfusion and more likely to have acquired it by intravenous drug abuse (P less than 0.05). All 13 patients with less severe chronic active hepatitis responded to interferon but only 5 of 15 patients with progressive fibrosis or cirrhosis responded (P less than 0.01). During 8-39 (median 19) months of observation of 16 untreated patients, there was a significant fall in antipyrine clearance (Cl-Ap) but no change in serum albumin. Among interferon-treated patients, Cl-Ap improved in 9 of 16 compared with 1 of 14 controls observed for the same time period (P less than 0.02). It is concluded that Cl-Ap is a sensitive test for detecting changes in liver function during chronic hepatitis. Without treatment, deterioration is evident at 18 months in 50% of patients with chronic active hepatitis C. Conversely, normalization of serum aminotransferase levels by interferon is associated with improvement of Cl-Ap.(ABSTRACT TRUNCATED AT 250 WORDS)