SUMMARY Hepatocytes isolated by the collagenase digestive method were transplanted into the spleens of syngeneic rats. Morphology and function of the hepatocytes in the spleen were investigated for 12 to 17 months after transplantation. The transplanted hepatocytes proliferated and reconfigured in the spleen without direct perfusion of portal venous blood and with the presence of an intact host liver. Fourteen to 17 months after transplantation, the hepatocytes which had formed a demarcated nodule occupied approximately 40% of the area of the splenic parenchyma without undifferentiation on microscopic examination. However, the weight of the hepatized spleen did not increase beyond the weight of a normal spleen and the weight of the host liver that had normal morphology also did not differ from a normal liver. Light and electron microscopic studies demonstrated differentiated cord structure and normal architecture for each heptocyte. Furthermore, the hepatized spleen synthesized albumin and glycogen as demonstrated by immunofluorescence and histochemical studies. Ammonia tolerance and indocyanine green clearance tests revealed functioning hepatocytes in the spleen proper. These results indicate that our experimental model lends itself well to investigations in cell growth mechanism and that hepatocellular transplantation has potential clinical application to compensate for impaired hepatic function Isolated cells, particularly isolated hepatocytes, are being used increasingly in studying cell growth and differentiation mechanisms and carcinogenesis. Isolated hepatocytes have several advantages as an in vitro cell culture system (1). However, the inevitable limitation of the system is that the cultured adult hepatocytes do not maintain their specific cellular functions and morphology for a long time (2). We previously reported that the splenic parenchyma was the most suitable location for the transplantation of isolated adult rat hepatocytes. These transplanted hepatocytes proliferated markedly in the spleen followed by reconfiguration for the following period of 10 months (3-5). The present study investigated the morphology and function of the transplanted hepatocytes in the rat spleen 1 year after transplantation