In order to study the role of the sympathetic nerves in the regulation of glucagon and insulin secretion, the distal stump of the left splanchnic nerve was electrically stimulated at the diaphragmatic level in the anesthetized dog under bilateral ligation of the adrenal veins. During stimulation, plasma glucose concentration rose rapidly, and pancreatic vein plasma concentration of glucagon increased along with pancreatic vein blood flow, indicating a greater output of glucagon. Insulin output in pancreatic vein plasma was slowly elevateddespite continued stimulation. Pretreatment with propranolol resulted in a decline of the basal output of both glucagon and insulin and in their marked initial fall at the onset of the stimulus. However, glucagon output still showed a vigorous increase during neural stimulation whereas insulin output remained totally suppressed, but showed a rebound rise after cessation of stimulation. Pretreatment with phentolamine evoked an enhancement in both basal output of insulin and its response to splanchnic stimulation, but did not exert any marked effect on glucagon output. Pretreatment with atropine inhibited the basal output of glucagon and insulin, but the response of insulin output to splanchnic stimulation wasnot suppressed, thus excluding the possibilitythat activation of aberrant parasympathetic nerve ffibers located in the splanchnic nerve would be responsible for the delayed increase in insulin release. The present results indicate that glucagons ecretion may be regulated by different receptor mechanisms from those involved in insulin release following sympathetic activation. (Endocrinology96:143, 1975)