The effect of bleeding against a predetermined pressure on the relative oxygen tension in the kidney was studied in rats anesthetized with either pentobarbital-Na or ethylurethane. In rats bled either for 30 min against 40 mm Hg or for 60 min against 50 mm Hg, the fall in the relative oxygen tension was significantly less during anesthesia with pentobarbital-Na, a highly potent protector against the occurrence of kidney lesions, than during anesthesia with ethylurethane, which possesses only slight protective potency. When rats anesthetized with ethylurethane were allowed to breathe oxygen the relative oxygen tension in the kidney was increased only for 15 to 20 min and accordingly the severity of the kidney lesions was decreased only when the animals were bled for 30 min at 40 mm Hg. When a number of different bleeding schedules were applied, a correlation was found between the average relative oxygen tension during bleeding and the incidence and degree of kidney lesions observed, irrespective of either the bleeding schedule or the anesthetic used. It is concluded that hypoxia may be a major factor in determining the occurrence of kidney lesions after bleeding and that the protective effect of anesthetics depends on their ability to diminish the fall in oxygen tension in the kidney during bleeding.