The superior cervical sympathetic ganglion is currently being used as a model neuronal system for the study of Ca2+-dependent processes in the mammalian nervous system. We have characterized a regenerative calcium conductance in postganglionic neurons. This Ca2+ current contributes to the shoulder of the action potential. In addition, Ca2+ influx during the spike activates a K+ conductance, which generates a hyperpolarizing afterpotential. These Ca2+-dependent potentials are antagonized by catecholamines. Pharmacologic studies suggest that alpha 2-adrenergic receptors inhibit the regenerative voltage-dependent Ca2+ influx that occurs during the action potential. Alpha-adrenergic agonists were also found to reduce the depression of the compound action potential following a train of preganglionic stimuli. We hypothesize that alpha 2-receptors function primarily to antagonize Ca2+ influx and thereby exert significant control over neuronal excitability and release of neurotransmitters.