Renal biopsies from 24 patients with oliguric "acute tubular necrosis" (ATN) and 26 patients with non-oliguric ATN were compared with biopsies from 7 patients who had recently recovered from ATN and 20 control patients. Many morphologic changes were present in the biopsies of patients with ATN and absent in controls, but only two lesions were significantly more severe in patients who had ATN at the time of the biopsy compared with patients who had recently recovered from ATN. These two lesions, necrosis of individual tubular epithelial cells and loss of brush border in proximal tubules, may play a role in the pathogenesis of renal functional failure in ATN. Necrosis of individual tubular epithelial cells appeared to be a continuing process. In the patients with non-oliguric acute renal failure there was a positive correlation between duration of renal failure and severity of tubular necrosis. This was not observed in the patients with oliguric acute renal failure, but otherwise there were no identifiable morphologic differences between the two groups. The glycerol model of acute renal failure in the rabbit was found to differ in several significant ways from ATN in man. Despite the fact that the rabbits had significantly less severe renal failure, their kidneys showed much more severe tubular necrosis and much more prominent presence of tubular casts than was the case in biopsies from patients with ATN. Loss of brush border in proximal tubules was not an important feature of the glycerol model of acute renal failure in the rabbit. We suggest that the glycerol model is not analogous to human ATN and may have an entirely different pathogenesis.