The concept of two types of alpha-adrenoceptor, alpha 1 located on smooth muscle and mediating contraction and alpha 2 located on nerve terminals and mediating inhibition of transmitter release, has broken down. In vivo it has been shown that post-junctional receptors, with characteristics closely related to those of the alpha 2-adrenoceptors at nerve terminals, can mediate pressor responses and are," post-junctional alpha 2-adrenoceptors". Several differences among agonists in vitro have superficial similarities to the in vivo alpha 1/alpha 2 system but do not correspond precisely and seem to point to a subdivision of post-junctional alpha 1-adrenoceptors. A preliminary hypothesis is: in vivo alpha 1 is rapid in onset, short-lived, utilises internal Ca2+, prefers alkalosis and responds to short-term stimuli such as short bursts of nerve impulses or bolus injections of catecholamines; alpha 2 is slower in onset, longer-lived, utilises external Ca2+, prefers acidosis and responds to more prolonged stimuli such as circulating catecholamines; in vitro these categories of response occur but antagonists fail to define an alpha 1/alpha 2 split, suggesting that some critical factor is missing in vitro. The implications of these trends in alpha-adrenoceptor classification are discussed in relation to current pharmacological and biochemical methods for receptor typing, to the possible physiological actions and roles of such receptors and to structure/activity relationships among agonists and antagonists.