Isolated syngeneic and allogeneic hepatocytes transplanted to spleen parenchyma are rapidly disintegrated. Host scavenger monocytes and macrophages are responsible for this reaction. We designed a method overcoming early disintegration of the intra-splenic grafted hepatocytes. It consisted of administration of anti-asialoGM I antiserum eliminating NK cells, sublethal whole body irradiation for depletion of scavenging cells and reconstitution with syngeneic bone marrow cells, ligation of host bile duct, intrasplenic hepatocyte transplantation and 3 consecutive partial hepatectomies. Six months after transplantation a glycogen-rich, trabeculae-forming, dividing hepatocytes, situated along strands of newly-formed fibrous tissue and numerous dilated blind bile canaliculae were observed. There was evidently more bile canaliculae in hosts with ligated bile duct than non-ligated controls. This is the first study showing fibrous tissue formed at the site of hepatocyte implantation and stellate cells are presumably responsible for this process.