The renal vascular system contributes in important ways to injury, dysfunction, and duration of ischemically induced and certain forms of nephrotoxic acute renal failure (ARF). Understanding injury to the renal vascular depends on an appreciation of the factors that control normal tone and reactivity in the kidney microvasculature. This is reviewed in some detail. Ischemia and ischemia-reperfusion not only cause substantial damage to the renal tubules, but cause frank injury to the vasculature as well. Vascular injury is mediated by oxidants, proteases, and cytokines that together alter basic properties of vascular function. There is an increase in intrinsic vascular tone that reduces glomerular filtration, and there is increased sensitivity to vasoconstrictor stimuli and altered autoregulatory capacity, which leave the kidney vulnerable to recurrent ischemic injury. Nonsteroidal antiinflammatory agents, radiocontrast media, and cyclosporine A cause ARF largely through their effects on the renal vasculature. Given these postischemic and toxic effects on the kidney microvessels, there is growing evidence that protection of the kidney from prolonged and recurrent injury depends on careful support of systemic hemodynamics and avoidance of injudicious use of vasoconstrictor agents.