Abstract: Synaptosomes prepared from rat cerebral cortex and labeled with [3H]noradrenaline (NA) were superfused with calcium-free Krebs-Ringer-bicarbonate medium and exposed to 10 mM K+ plus 0.1 mM Ca2+ so that [3H]NA release was induced. 6,7-Dihydroxy-N,N-dimethyl-2-ami-notetralin (TL-99) strongly inhibited synaptosomal K+-in-duced [3H]NA release (EC50= 5–10 nM) by activating α2-adrenoceptors. Release was also inhibited (maximally by 40–50%) by morphine (EC50= 5–10 nM), [Leu5]enkephalin (EC50=∼300 nM), [d-Ala2,d-Leu5]enkephalin (DADLE), and Tyr-d-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) (EC50 values =∼30 nM). In contrast to the μ-selective opioid receptoragonists morphine and DAGO, the highly δ-selective agon ist [d-Pen2, dPen5]enkephalin (1 μM) did not affect [3H]-NA release. Furthermore, the inhibitory effect of DADLE, an agonist with affinity for both δ-and μ-opioid receptors, was antagonized by low concentrations of naloxone. The findings strongly support the view that, like α2-adrenocep-tors, μ-opioid receptors mediating inhibition of NA release in the rat cerebral cortex are localized on noradrenergic nerve terminals.