Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic disease. We observed 3 patients in whom chronic GVHD of the liver after allogeneic nonmyeloablative hematopoietic stem cell transplantation (HSCT) presented with marked elevations of serum aminotransferases, clinically resembling acute viral hepatitis. The liver biopsies revealed predominant diffuse lobular injury and degenerative small bile ducts. Prompt administration of high-dose immunosuppressive therapy achieved a rapid improvement of liver enzymes and bilirubin levels. We conclude that a distinct syndrome of chronic hepatic GVHD presenting as an acute hepatitis should be considered as one possible explanation for hepatic dysfunction in patients who receive nonmyeloablative allogeneic HSCT.