There is a paucity of data regarding hepatic allograft iron accumulation in patients undergoing orthotopic liver transplantation (OLT) in whom severe iron overload was present in the native explanted liver. Our aim is to evaluate the frequency and cellular distribution of stainable iron in early and late post-OLT hepatic allograft biopsy specimens from patients undergoing their first OLT who had excess iron in their native explanted liver. We compared iron-staining patterns in hepatic allograft biopsy specimens at approximately 1 month (early) and 1 to 2 years (late) post OLT in 41 patients with hepatic iron indices greater than 1.9 in the explanted liver (cases) with a selected group of matched controls without explant hemosiderosis. Our cases included 6 patients with a pre-OLT diagnosis of hereditary hemochromatosis and 35 patients with cirrhosis and secondary iron overload. Early iron deposition was mild in most cases, commonly affected Kupffer's cells, and was seen with similar frequency in cases and controls (41% v 27%; P =.29). Stainable iron was observed in 20 donor livers (12 cases, 8 controls), and all 20 subjects showed stainable iron in 1-month hepatic allograft biopsy specimens. Liver samples from 35 matched pairs were studied for late iron deposition. Iron deposition was observed in 43% of cases versus 17% of controls (P =.06). In conclusion, the frequency of stainable iron in early hepatic allograft biopsy specimens was not different between patients with versus without pre-OLT hepatic hemosiderosis. There was a suggestion that patients with severe pre-OLT hemosiderosis had a greater frequency of iron accumulation in late hepatic biopsy specimens.