The contribution of exocytosis to norepinephrine-stimulated prostaglandin release from sympathetic postganglionic neurons was evaluated in homogenates of adult rat superior cervical ganglia. Incubation of ganglion homogenates with norepinephrine (1 mM) for 30 min caused an increased release of prostaglandin E2 and prostaglandin I2 (measured as the stable metabolite, 6-keto-PGF1a). Neither tetrodotoxin (10 mM), K+ (120 mM), nor EDTA in Ca(2+)-free buffer affected prostaglandin generation under basal and norepinephrine-stimulated conditions. These results suggest that the increase in prostaglandin production by sympathetic neurons after norepinephrine administration is not through the release of previously synthesized intracellular stores. Instead, the increase in prostaglandins in response to norepinephrine appears to be explained by de novo synthesis.