The present study was conducted to investigate how the in vivo glucagon secretory response to 2-deoxy-D-glucose relates to control of nervous system. Plasma glucagon levels in the rat were significantly elevated by 2-deoxy-D-glucose administration (40 mg/100 g body weight). That response was suppressed by hexamethonium, a nicotinic ganglionic blocker. By contrast, treatment with atropine (5 mg/100 g body weight), a muscarinic antagonist, had no effect on glucagon secretion due to the same dose of the deoxysugar, whereas the drug totally inhibited the response to a lower concentration of the deoxysugar. Administration of 2-deoxy-D-glucose significantly elevated plasma epinephrine levels, and it was suppressed by hexamethonium. Plasma insulin levels were not so changed despite hyperglycaemia. In conclusion, the present study suggests that 2-deoxy-D-glucose may act on cholinergic nerve system to stimulate the release of glucagon and epinephrine.