A sensitive and specific radioimmunoassay for human ligandin has been developed and used to study ligandin release into the serum in acute and chronic hepatitis. Serum ligandin concentrations were elevated in 67 of 68 cases of acute viral hepatitis. Ligandin levels frequently returned to normal within the first 2 weeks of illness. The rapid disappearance of ligandin preceded the return to normal of serum SGOT. In chronic active hepatitis, serum ligandin levels correlated significantly (p < 0.01) with histologic severity of disease. This correlation was not seen with SGOT. Serum ligandin may be useful in monitoring progress and the need for therapy in chronic active hepatitis.