The present study was performed to establish whether sequential determinations of antipyrine clearance, using a simplified two-point test, are sensitive and specific indicators of changes in chronic hepatitis B disease activity. Sixteen patients were studied on four or more occasions during 18 to 30 months. Eleven patients were treated with recombinant human α-interferon (2.5, 5.0 or 10 × 106 per m2, intramuscularly, three times per week, for 24 weeks), and five patients were untreated controls. Among seven patients, (six interferon-treated and one control) who lost hepatitis B e antigen from serum, antipyrine clearance improved by 46% (range: 20 to 160%) from 0.37 ± 0.14 ml per kg per min (mean ± S.D.) to 0.54 ± 0.13 ml per kg per min, p < 0.005. This change paralleled the loss of symptoms and reduction of serum ALT levels (from 206 ± 189 IU per liter (mean ± S.D.) to 38 ± 12 IU per liter, p < 0.005). Conversely, antipyrine clearance declined to previous levels when reactivation of chronic hepatitis B with reappearance of HBeAg in serum occurred. Regardless of changes in hepatitis B serology, when serum ALT values fluctuated by more than 20% (presumed to reflect fluctuations in necroinflammatory activity of the liver disease), antipyrine clearance also changed whereas serum albumin and bilirubin concentrations and prothrombin time did not. It is concluded that antipyrine clearance is a more sensitive and specific parameter than conventional indices for assessing hepatic metabolic function during changes in chronic hepatitis B disease activity. Remission in disease with loss of HBeAg from serum is associated with improved hepatic metabolic function as determined by the antipyrine clearance test.