The effect of sodium DL-lactate administration on insulin release in anesthetized dogs has been studied. Eleven mongrel dogs were infused with sodium DL-lactate for 20 min at the rate of 20 mg/kg . min. Lactate infusion produced simultaneous increases in blood glucose and plasma insulin levels in the pancreaticoduodenal vein. To determine whether lactate stimulated insulin secretion directly, sodium DL-lactate was rapidly injected into the pancreatic artery of six dogs; this pulse induced a significant increase in insulin release from pancreatic B-cells, even in the absence of a measurable change in blood glucose. Diazoxide, when infused in six dogs, blocked lactate-induced insulin secretion. These findings indicate that lactate, as do other circulating energy fuels, may play a role in the physiologic control of insulin secretion.