Despite the availability of modern techniques, mortality continues to be high in acute renal failure (ARF). A more specific form of therapy will not be available until the basic pathophysiologic mechanisms in ARF are known. Tubular obstruction, increased tubular permeability and marked renal hemodynamic alterations are major mechanisms that have been proposed and investigated. Evidence has been obtained suggesting that tubular obstruction by interstitial edema or intratubular casts and "passive backflow" due to increased tubular epithelial permeability do not have primary roles in ARF, although they may augment the degree of renal insufficiency. The majority of recent studies indicate that alterations in renal hemodynamics, mediated by the renin-angiotensin system, are responsible for the near cessation in glomerular filtration observed in ARF. A schema for the pathogenesis of ARF, with therapeutic implications, has been developed.