The effect of insulin-induced hypoglycemia upon plasma arginine vasopressin measured by a specific and sensitive RIA has been studied in unanesthetized male Sprague-Dawley rats. Hypoglycemia caused a 5-fold rise in plasma arginine vasopressin to a maximum of 28.0 +/- 9.1 pg/ml (mean +/- SD). This response was associated with a 2% fall in plasma osmolality, a rise in plasma sodium of less than 1%, a 10% fall in estimated blood volume, and no significant change in mean arterial blood pressure. PRA was increased 5-fold by hypoglycemia. However, beta-adrenergic blockade with propranolol completely prevented the renin response without altering the rise in vasopressin. In contrast, water loading abolished and hypertonic saline loading enhanced the effect of hypoglycemia on plasma vasopressin. We conclude that insulin-induced hypoglycemia stimulates vasopressin secretion by some as yet unrecognized primary mechanism whose responsiveness can be altered by changes in osmolality.