To investigate the receptors mediating the regulation of norepinephrine (NE) release in human cerebral cortex slices, we examined the effects of opioid agonists for μ-, δ-, and κ-receptors on the high potassium (15 mM)-evoked release of [3H]NE. [3H]NE release induced by high potassium was calcium-dependent and tetrodotoxin-sensitive. [D-Pen2, D-Pen5]enkephalin (DPDPE) and deltorphin II (Delt II) inhibited the stimulated release of norepinephrine in a dose-dependent manner. However, Tyr-D-Ala-Gly-(Me)Phe-Gly-ol and U69,593 did not influence the NE release. Inhibitory effect of DPDPE and Delt-II was antagonized by naloxone, naltrindole, 7-benzylidenaltrexone and naltriben. These results suggest that both δ1 and δ2 receptors are involved in regulation of NE release in human cerebral cortex.