NH₄CI was infused into the left renal artery of anesthetized dogs at 50–125 µM/kg/min for up to 110 min. Renal blood flow declined early then increased to supra-control levels during infusion. Kidneys perfused at 125 µM/kg/min for 90 min showed patchy to confluent mixtures of cortical necrosis and tubular necrosis. Experimental kidneys invariably showed lower urine osmolality than contralateral controls 48 h after perfusion. Kidneys with necrosis showed depressed creatinine clearance as well. Renal artery infusion of NH4 acetate or intravenous infusion of NaHCO₃ during arterial infusion of NH₄CI prevented significant acidosis and caused minimal histological changes, but depression of urine osmolality was not prevented. It is concluded that renal ammonium concentrations up to 40 µM/liter for 90 min does not cause tubular necrosis but does impair urine concentration. Severe tissue damage followed renal exposure to high ammonium concentrations in the presence of metabolic or renal acidosis.