Naked plasmid DNA in hypertonic solutions was injected intraportally in mice whose hepatic veins were transiently occluded. High levels of luciferase expression and beta-galactosidase expression in 1% of the hepatocytes throughout the entire liver were achieved using 100 micrograms of the respective plasmid vector. Two days after the intraportal injection of 100 micrograms of pCMVGH, the mean hGH serum concentration was 65 ng/ml +/- 26 (n = 7) which is approximately 50-fold above normal baseline levels. These unprecedented levels of foreign gene expression from naked plasmid DNA document the ability of parenchymal cells in vivo to take up naked DNA following intravascular delivery.