We have used high-titer (10(8) ffu/ml) recombinant retroviral vectors to transfer the beta-galactosidase (beta-Gal) gene to rat hepatocytes in vivo. In animals injected twice in the portal blood stream the next day after partial hepatectomy, half of the hepatocytes (46 +/- 17%) expressed the marker at the end of liver regeneration. The number of positive cells closely correlated with the viral titer as well as with beta-Gal enzymatic activity present in the whole liver. Because genes transferred via retroviral vectors in the liver are known to be expressed permanently, our present results open new possibilities for the development of gene therapy protocols for hereditary liver diseases using recombinant retroviral vectors.