The study aim was to investigate the role of the parasympathetic nervous system in the control of glucose tolerance in man. Glucose kinetics were determined during an oral glucose tolerance test (OGTT) in six subjects with truncal vagotomies and six control subjects. Basal plasma glucose levels in the two groups were equal; however, 20 to 40 minutes after the OGTT, glucose was higher in vagotomized compared with control subjects (P < .02). There were no differences in insulin levels between the subjects. Glucagon decreased after the OGTT in the controls, whereas in the vagotomized subjects it increased transiently and did not decrease beyond basal levels. There was no difference in basal hepatic glucose production, but suppression was greater in controls in the first 10 minutes (P < .01). Gut-derived glucose appearance increased faster and to a higher level (56.0 +/- 8 v 29.7 +/- 2.9 mumol/kg/min, P < .02) in vagotomized subjects. There were no differences in the metabolic clearance rate of glucose between the two groups. It is concluded that parasympathetic innervation of the pancreas is essential for suppression of glucagon secretion during hyperglycemia. However, abnormal glucose tolerance in vagotomized subjects is primarily due to rapid gut glucose absorption, with the denervated parasympathetic system playing only a minor role.