Over the last few years several groups have used retroviral vectors to achieve stable gene transfer into endothelial cells. In vitro experiments include transduction of cultured cells with genes of potential therapeutic interest, such as growth hormone and tissue plasminogen activator (t-PA). Animal studies have demonstrated the feasibility of in vivo recombinant gene expression from transduced endothelial cells, but have thus far been accomplished only with the lacZ marker gene. All studies to date have been oriented primarily toward the use of transduced endothelial cells to provide gene therapy. Numerous issues remain to be addressed with experimental data prior to the initiation of a clinical protocol using transduced endothelial cells. These issues include the introduction of larger numbers of transduced cells into the vasculature and the achievement of appropriate regulation of transgene expression. The use of retroviral vectors to study basic endothelial cell biology has been relatively ignored. The tool of retroviral vector-mediated gene transfer is available for use in answering both therapeutic and pathophysiological questions in endothelial cell biology.