Staircase increments of Ca (from 0.5 to 15 meq/l) were added to the perfused rat pancreas in the absence of glucagon secretogogues. Large spikes of glucagon release resulted, particularly at the small and large Ca concentrations. Insulin secretion was undetectable. Selective destruction of peripheral adrenergic neurons by pretreatment of the rats with 6-hydroxydopamine reduced the basal glucagon secretion to about 50% and specifically suppressed the Ca-induced glucagon release at the lower Ca steps. The response to a subsequent stimulation by arginine/Ca was not inhibited. Glucagon secretion probably is modulated by a stimulant effect of the pancreatic adrenergic nerves (norepinephrine?) and Ca in part positively affects release by permitting this neural stimulation.