ABSTRACT— For determination of the most suitable tissue for heterotopic transplantation of exogenous hepatocytes, dissociated hepatocytes or small pieces of liver tissue were transplanted into the spleen, adipose tissue and inside the capsule of the kidney of BALB/c mice. Survival of syngeneic grafts of dissociated hepatocytes was highest in the spleen and that of pieces of liver tissue in the adipose tissue, but only the latter system was suitable for xenogeneic transplantation. Histological examination showed that a total of 50% of the human or duck liver tissue implants survived in the inguinal fat pad of athymic nude mice (BALB/c-nu). Histochemical analyses revealed that most hepatocytes transplanted into the fat pad gave positive reactions for glucose-6-phosphatase and with periodic acid-Schiff reagent at least 28 days after transplantation. Electron microscopic observation showed that these cells also maintained characteristic cellular organelles. This xenogeneic transplantation into adipose tissue should be useful in the studies on replication and infection of human hepatotropic viruses such as hepatitis B and C viruses.