We describe here the development and testing of simian virus 40 (SV40)-derived vectors to deliver foreign genetic material to the liver. Based on current understanding of the biology of wild-type SV40, it should be possible to exploit several important attributes of this virus, including efficient replication and gene expression, almost universal infectivity, and low immunogenicity if large T-antigen is deleted, to deliver DNA to the liver effectively. Our studies in cultured hepatocytes and in vivo, using both reporter constructs and transgenes of therapeutic interest, provide strong experimental support for this prediction. These successes indicate that SV40 may play an important role in gene delivery to the liver.