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Functional human hepatocytes xenografted into the liver of mice can be used as a model system to study pharmacokinetics, infection of hepatitis viruses, and the efficacy of hepatitis vaccines. Significant levels of liver xeno-repopulation have been reported in Fah Rag2 Il2rg mice. However, the high mortality and low breeding rate of this model may hinder its application. A new model, termed Fah Nod/Scid mice, which combines the advantages of liver repopulation in Fah mice with the ease of xenotransplantation in Nod/Scid mice was obtained by gradual cross-breeding. Fah Nod/Scid mice were easily maintained in breeding colonies and in adult animal care facilities. FK506 treatment combined with gradual withdrawal of NTBC before cell transplantation ensured that Fah Nod/Scid mice were susceptible to liver xeno-repopulation by human hepatocytes; the proportion of engrafted human hepatocytes reached 33.6%. The function of the expanded human hepatocytes within the chimeric liver was confirmed by weight curve analysis, the expression of characteristic proteins, and the biochemical analysis of liver function. These results show that Fah Nod/Scid mice are an ideal humanized liver mouse model with many useful applications. [ABSTRACT FROM AUTHOR]