Most alpha 2-adrenoceptor agonists developed so far will penetrate into the brain, thus causing central hypotensive activity, mediated by the stimulation of alpha 2 adrenoceptors in the region of the nucleus tractus solitarii, the vasomotor center and the nucleus of the vagus nerve. The central alpha 2 adrenoceptors are probably located at postjunctional (postsynaptic) sites. Their stimulation causes sympathoinhibition and thus a decrease in blood pressure and heart rate. The central hypotensive effect is the dominating activity of all alpha 2-adrenoceptor agonists developed so far, of which clonidine, guanfacine and alpha-methyl-DOPA (which is converted into alpha-methyl-noradrenaline) are the prototypes. Peripheral postsynaptic effects probably do not greatly contribute to the hypotensive activity of these drugs. Sedation, also mediated by central alpha 2 adrenoceptors is the major adverse reaction to these antihypertensive agents. More selective alpha 2-adrenoceptor agonists (B-HT 920, azepexole, UK 14,304) appear to display the same pattern of hypotensive and sedative activities as the nonselective compounds like clonidine. After the general survey on centrally acting alpha 2-adrenoceptor agonistic drugs, the pharmacologic profile of the new oxazoline derivative, rilmenidine, (S 3341) was compared with that of the classic compound, clonidine. In all current animal and in vitro models, rilmenidine was characterized as a clonidine-like, centrally acting antihypertensive drug. Thus, its central hypotensive activity proved mediated by the stimulation of central alpha 2 adrenoceptors. In radioligand binding studies, rilmenidine proved somewhat more selective for alpha 2 adrenoceptors, but this selectivity was not reflected by a clearly different pharmacologic profile of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)