Although on the average aortic endothelium is a highly stable tissue, available data indicate that there are areas of high, spontaneous, focal cell turnover. This may be significant since the response to experimental endothelial denudation includes thrombosis and smooth muscle proliferation, both components of atherosclerosis lesion formation. Thus questions about mechanisms of endothelial injury and about the role of the repair process in maintenance of endothelial integrity are likely to be important in attempting to understand the pathogenesis of atherosclerosis. Our approach is to ask what factors control endothelial regeneration. Studies include both in vitro and in vivo data. Regeneration in vivo is strongly dependent on the geometry of the vessel; recovery is much more rapid along the vessel axis. This appears to explain the localization of smooth muscle lesions following mechanical removal of the endothelium, since rapidly recovered areas do not develop smooth muscle proliferation. In vitro, regeneration is independent of a requirement for growth factors, implying that the signal for this process is intrinsic to the monolayer. Cytochalasin B inhibits both movement and replication, implying that movement may be required for transition from G0 to G1. Finally, we have discovered that cultured endothelial cells themselves produce a growth factor. This is of potential importance for interactions between smooth muscle cells and endothelial cells in the vascular response to injury.