Basic fibroblast growth factor (bFGF) and transforming growth factor-alpha (TGF alpha) have been identified as potent hepatotrophic mitogens. bFGF and TGF alpha induce DNA synthesis in fetal and adult rat hepatocytes in primary culture and support fetal rat hepatocyte multiplication in chemically defined medium. No additional exogenous growth or progression factors are required by the cells for traversing the cell cycle or for cell division. These mitogenic polypeptides, previously identified in various cell types including liver and endothelial cells, platelets, and macrophages may act locally in a paracrine mode in controlling hepatocyte multiplication in the liver during development and regeneration.