Cells within pineal glands isolated from young, male guinea pigs were impaled with intracellular microelectrodes and their responses to stimulate the nerve supply to the gland were studied. Two types of cells were identified. The response of cells of type I was a depolarization on which spikes were superimposed. Blockers of alpha-adrenoceptors abolished the spikes while beta-adrenoceptor blockers reduced the depolarization to 27%, leaving a small tetrodotoxin-sensitive depolarization. After bilateral removal of the superior cervical ganglia (SCG) the beta-mediated depolarization was not observed while the spikes and the smaller depolarization persisted. The response of cells of type II was an initial large, transient depolarization followed by a smaller depolarization. Both components were reversibly blocked by tetrodotoxin. The only agents found to have any effect on these cells were oxytocin, vasopressin, and vasotocin. These peptides caused depolarization similar in amplitude to the larger response to nerve stimulation, although more prolonged. The large depolarization was not observed following ganglionectomy, but the smaller one persisted. It is concluded that cells of type I and II both receive inputs from nerves whose cell bodies lie in the SCG. Cells of both types are also innervated through another pathway.