The effect of the cephalic phase of food ingestion on plasma insulin and glucagon concentration was assessed in the sham-feeding rat, bearing chronically implanted gastric drainage fistulas. It was found that continuous sham feeding produced a significant and phasic peripheral insulin response in the absence of any significant changes of glycemia. The response was almost completely blocked by prior intravenous administration of 2 mg/kg of atropine methyl nitrate and potentiated by prior intravenous administration of 1.0 or 2.5 mg/kg of phentolamine. In spite of the larger insulin response after phentolamine, there was no hypoglycemia detected. Furthermore, continuous sham feeding did not produce a significant glucagon response, whereas real feeling did. The results demonstrate that cholinergic insulin release is triggered phasically by continuous ingestion of familiar food and that this insulin response is inhibited by an alpha-adrenergic sympathetic tone. It is further concluded that the increased glucose disposal produced by the neurally released insulin is not counteracted by a concomitant glucagon response or by direct adrenergic stimulation of hepatic glucose production.