Retroviral vectors can be used to transfer genes effectively into cell lines and primary cells. Less is known, however, whether these vectors can be used to transfer genomic genes into tissue culture cells and animals to yield tissue specific expression of the transferred gene. We have now shown, that retroviral vectors carrying the human beta-globin gene can lead to regulated expression of human globin RNA and protein in murine erythroleukemia cells. In addition, we have recently designed a new high titer ecotropic retroviral vector that has been used to transfer the human beta globin gene into CFU-S murine spleen colonies. The human beta globin gene is expressed in a vast majority of the CFU-S colonies indicating preferential integration at transcriptionally active sites. The expression level of the transferred human beta globin gene was found to be 1-5% of the mouse beta globin genes. Infected bone marrow was transplanted into genetically anemic W/Wv mice resulting in production of human beta globin chanins in circulating red cells between 3 and 8 weeks post-transplantation. Two animals have been detected so far that have human beta globin production more than 3 months after transplantation indicating successful gene transfer into long-term reconstituted animals.