A n experimental model of postischemic, acute renal failure has been developed in Wistar rats with surface glomeruli, thereby making possible a direct assessment of the mechanisms responsible for the fall in glomerular filtration rate that characterizes this disorder. Whole kidney and cortical single nephron filtration rates were reduced proportionately, on average by approximately 40%, after 3 h of nearly complete occlusion of the ipsilateral renal artery. The possibility of a significant transtubular leak of inulin was excluded. This decline in filtration rate occurred in the absence of measured changes in mean arterial pressure, mean glomerular transcapillary hydrostatic pressure, or net ultrafiltration pressure at afferent and efferent ends of the glomerular capillary. Net ultrafiltration pressure at the efferent end of the capillary approached zero both before and after ischemic injury, demonstrating that filtration pressure equilibrium was achieved throughout this study. Single nephron filtration fraction remained unchanged, indicating that the fall in filtration rate was accompanied by a proportional decline in glomerular plasma flow. The results indicate that the fall in filtration rate was solely the consequence of this fall in glomerular plasma flow. Since filtration rate per nephron is equal to the product of the ultrafiltration coefficient and mean ultrafiltration pressure, this product must also have fallen in proportion to the decline in glomerular plasma flow. Evidence is presented to indicate that a change in ultrafiltration coefficient is not required to account for the observed fall in filtration rate. The reduction in glomerular plasma flow, occuring in the absence of a concomitant decline in mean glomerular capillary hydrostatic pressure, resulted from large and proportional increases in afferent and efferent arteriolar resistances. These resistance changes appear to play a fundamental role in the pathogenesis of this form of acute renal failure.