The influence of insulin in the cephalic phase of postprandial thermogenesis was investigated in dogs. O2 consumption (VO2) and respiratory quotient (RQ) were continuously monitored 1 h before and 2 h after a 1,015-kcal meal during a control, an atropine, or a pancreatic-denervation experiment. A first phase (cephalic phase) in VO2 increase, lasting at least 50 min, followed by a second phase (digestive phase) were found in the control experiment. During both the atropine and pancreatic-denervation experiment, the first phase of VO2 was inhibited by 52%. The second phase was completely abolished with atropine, whereas it remained comparable to the control in the case of pancreatic denervation. A peak increase for insulin (70 microU/ml over 0 time) was observed 2 min after the onset of feeding in control. It was followed after 25 min by a second increase related to changes in glycemia. Maximal rises of norepinephrine (NE) and epinephrine corresponded to 215 and 120 pg/ml above basal values at 2 min in control experiment. During both atropine and pancreatic denervation the cephalic phase of insulin release was suppressed and the NE increase was inhibited by congruent to 65%. During the digestive phase pancreatic denervation caused an increase in plasma insulin comparable to that of the control, whereas atropine produced no such effect. It is suggested that the cephalic phase of postprandial thermogenesis is mediated through a causal relationship between insulin and NE release.