The knowledge on alpha-adrenoceptors has expanded enormously in the last decade, mostly as a result of in vitro and in vivo animal experiments. In the face of considerable species differences we have tested several of the newly developed concepts on alpha-adrenoceptors in the circulation of the human forearm. In this model we were able to show the presence of postsynaptic alpha 1- and alpha 2-adrenoceptors, both contributing to resting vascular tone. Although adrenaline and noradrenaline were shown to have affinity for each alpha-adrenoceptor subtype, noradrenaline seems to be the natural agonist for both receptors. Evidence is presented for an intrasynaptic location of the alpha 1-adrenoceptor and an extrasynaptic location of the alpha 2-adrenoceptor and also for a functional presynaptic alpha 2-adrenoceptor in the human forearm circulation. Selective hyperresponsiveness to alpha 1- or alpha 2-adrenoceptor stimulation in hypertensive patients could not be established. Calcium entry blockers were shown to attenuate the vasoconstriction induced by selective alpha 2-adrenoceptor stimulation but not by selective alpha 1-adrenoceptor stimulation. These data support the physiological and pharmacological relevance of the new concepts on alpha-adrenoceptors for the situation in man.