Although fibroblast growth factor 1 (FGF-1) (formerly known as acidic FGF) but not FGF-2 (or basic FGF), has been suggested to play a pathophysiological role in liver regeneration, its clinical application has been restricted by its limited mitogenecity and heparin dependence. We report here that a chimeric human FGF protein, FGF-C(1211), is a heparin-independent potent mitogen for liver parenchymal cells both in vitro and in vivo. In the presence of serum and physiological concentration of insulin, FGF-C(1211) by itself induces as much as 55% of hepatocytes in culture to proliferate and up to 88% when used in combination with hepatocyte growth factor or epidermal growth factor. Furthermore, hepatocytes nuclear labeling in vivo with bromodeoxyuridine was markedly enhanced when FGF-C(1211) was injected intravenously into carbon tetrachloride-administered mice. Because FGF-C(1211) is heparin independent and nonantigenic, it has potential for clinical and preclinical applications.