Serum thyroid hormones and thyroid hormone binding were sequentially measured in 20 patients with acute hepatitis B infection. Criteria to select patients consisted of a positive test for hepatitis B surface antigen, aspartate aminotransferase (AsAT) concentration greater than 400 U/L during the acute illness, and available serum specimens after recovery. The mean serum thyroxine (T4) concentration (+/- SE) was 12.5 +/- 0.6 microgram/dL during acute infection and 7.4 +/- 0.3 microgram/dL after recovery (p less than 0.001), whereas mean free T4 index values did not significantly differ. The mean serum thyroxine-binding globulin (TBG) concentration was significantly increased (p less than 0.001) during acute illness and accounted for the reversible of serum and the increased serum T4 concentrations. The rise in serum TBG correlated with the rise in AsAT during the acute illness (p less than 0.04) suggesting nonspecific release of these proteins from injured hepatocytes. The mean free triiodothyronine (T3) index was decreased during acute hepatitis (p less than 0.001) and returned to normal after recovery, indicating that acute hepatitis B infection, like other nonthyroidal illnesses, is associated with decreased T4 to T3 conversion in peripheral tissues.