Some aspects of the physiological regulation of the pineal alpha 1-adrenoceptor have been studied using the selective, high-affinity ligand [125I] iodo-2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone ([125I]HEAT). Pineal glands taken from rats housed in a diurnal lighting cycle showed no circadian rhythm in the number of specific [125I]HEAT binding sites, although a characteristic rhythm in pineal melatonin was seen. It was established that the pineal alpha 1-adrenoceptor is under neural control because interruption of neural stimulation of the pineal by bilateral superior cervical ganglionectomy (SCGX) or by exposing rats to constant light for 3 weeks doubled receptor density but did not change affinity for [125I]HEAT. Administration of various alpha 1-adrenoceptor agonists either acutely (i.p. injection) or chronically (s.c. infusion) did not alter the number of specific [125I]HEAT binding sites. Together these results indicate that the pineal alpha 1-adrenoceptor, like the pineal beta-adrenoceptor, is regulated by sympathetic nerve activity, probably through the physiological release of the neurotransmitter norepinephrine. However the absence of a circadian rhythm in alpha 1-adrenoceptor number and lack of down-regulation by adrenergic agonists imply different mechanisms of regulation.