Hepatocyte growth factor is a protein growth factor with a strong mitogenic effect on hepatocytes. Recently, hepatocyte growth factor and hepatocyte growth factor messenger RNA have been extracted from several organs of humans, rats and rabbits. This study was undertaken to comprehensively define and compare the cellular localization of hepatocyte growth factor in human and rat tissues in detail. Paraffin-embedded sections and frozen sections were examined by immunohistochemistry using a polyclonal antiserum to hepatocyte growth factor. The distribution of hepatocyte growth factor was almost identical in humans and rats. Strong or moderate cytoplasmic immunoreactivity for hepatocyte growth factor was present in most surface epithelia, distal tubules and collecting ducts of the kidneys, large neurons, megakaryocytes, granulocytes, exocrine pancreas, salivary glands, prostate, epididymis and trophoblast. Varying degrees of immunoreactivity were observed in endothelial cells, chondrocytes and macrophages. We conclude that hepatocyte growth factor is widely distributed in numerous tissues and cell types independent of their regenerative activity. This suggests that hepatocyte growth factor may have mitogenic and/or trophic effects on multiple cell types in addition to hepatocytes.