AIM To investigat the influence of hemochromatosis gene(Hfe)mutation on 59Fe labelled duodenal heme absorption in mice.METHODS Heme absorption was measured in Hfe wild type and Hfe(-/-)mice by the duodenal tied loop and by oral gavage methods.The mRNA expression of heme oxygenase(HO-1),Abcg2 and Flvcr1 genes and levels were determined by quantitative polymerase chain reaction.RESULTS Heme absorption was significantly increased in homozygous Hfe(-/-)mice despite significant hepatic and splenic iron overload.While duodenal HO-1 mRNA was highly expressed in the wild type and Hfe(-/-)heme-treated group following 24 h heme administration,Flvcr1a mRNA decreased.However,Abcg2 mRNA expression levels in duodenum remained unchanged.CONCLUSION Heme absorption was enhanced in Hfe(-/-)mice from both duodenal tied-loop segments and by oral gavage methods.HO-1 mRNA levels were enhanced in mice duodenum after 24 h of heme feeding and may account for enhanced heme absorption in Hfe(-/-)mice.Implications for dietary recommendations on heme intake by Hfe subjects to modulate iron loading are important clinical considerations.