The effects of hypoglycemia on cerebrovascular permeability to the Evans blue-albumin complex were studied in rats injected with 50 IU/kg, i.v. crystalline zinc insulin. One group of hypoglycemic animals was warmed to keep their body temperatures close to 37 degrees C, and the rats in the other group were allowed to become hypothermic by hypoglycemia. The arterial blood pressures of the hypoglycemic rats were continuously monitored during the coma and a significant rise in pressure was observed in most animals at the end of the coma. When glucose was administered i.v. to five animals of each group, this elevated pressure returned to normal values within 0.5 min and the animals slowly recovered normal behavior. At termination of the coma, most brains in the hypothermic hypoglycemic group showed an intensive and extensive staining by Evans blue; whereas only two brains in the normothermic hypoglycemic group showed any noticeable extravasation of Evans blue-albumin. Arterial PO2, PCO2, and pH were determined and no significant difference was found between values from animals in hypoglycemic coma and the controls. Four animals were surface-cooled and were used to examine the effects of hypothermia on blood-brain barrier permeability. These brains did not show any macroscopically evident Evans blue-albumin extravasation. The results indicated that prolonged, severe hypoglycemia with hypothermia caused a profound blood-brain barrier dysfunction whereas normothermic hypoglycemia resulted in few cases of any noticeable increase in blood-brain barrier permeability.