Nicotinic transmission in the superior cervical ganglion of the cat was studied in vivo and in vitro by recording the postganglionic compound action potential evoked, under partial block with hexamethonium, by supramaximal 0.2 Hz stimulation of the cervical sympathetic trunk. The compound action potential was depressed following a stimulus train (5 Hz, 40 s) applied to the same set of axons. The inhibition was antagonized by naloxone, suggesting mediation by endogenous opioids. Agonists selective for mu-, delta- and kappa-opioid receptors, injected into the arterial supply of the in situ ganglion or added to the perfusion fluid in the in vitro ganglion, also produced a naloxone-sensitive inhibition of the compound action potential. The synaptic inhibition was antagonized by the delta-selective antagonist ICI 174,864 and by the mu-selective antagonist CTAP, but not by the kappa-selective antagonist Nor-BNI. These results suggest that all three main types of opioid receptors are present in the ganglion but only mu- and delta-receptors are involved in the inhibition of ganglionic transmission mediated by the endogenous opioids.