A 38-yr-old woman with liver disease due to protoporphyria underwent orthotopic liver transplantation. The resected liver was cirrhotic and contained a massive amount of protoporphyrin, with numerous birefringent pigment deposits. Transplantation was accomplished without difficulty following blood volume exchange to reduce the blood protoporphyrin level. Sequential biopsy specimens obtained through the 13th month after transplantation showed no accumulation of protoporphyrin pigment deposits in the new liver. Portal inflammation observed in the liver biopsy specimen at 6 mo after transplantation resolved spontaneously. Erythrocyte and serum protoporphyrin levels returned to values similar to those in the pretransplantation period when the patient had normal hepatic function; the fecal level was lower. Thus orthotopic liver transplantation can be successfully done in patients with protoporphyria who have severe liver disease. Prolonged follow-up is needed to determine the ultimate outcome, however, as the new liver remains susceptible to protoporphyrin-induced damage.