Most α 2-adrenoceptor agonists developed so far will penetrate into the brain, thus causing central hypotensive activity, mediated by the stimulation of α 2 adrenoceptors in the region of the nucleus tractus solitarii, the vasomotor center and the nucleus of the vagus nerve. The central α 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 α 2-adrenoceptor agonists developed so far, of which clonidine, guanfacine and α-methyl-DOPA (which is converted into α-methylnoradrenaline) are the prototypes. Peripheral post-synaptic effects probably do not greatly contribute to the hypotensive activity of these drugs. Sedation, also mediated by central α 2 adrenoceptors is the major adverse reaction to these antihypertensive agents. More selective α 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 α 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 α 2 adrenoceptors. In radioligand binding studies, rilmenidine proved somewhat more selective for α 2 adrenoceptors, but this selectivity was not reflected by a clearly different pharmacologic profile of the drug. However, rilmenidine greatly differs from clonidine with respect to sedative activity, which could not be demonstrated even for high doses of rilmenidine in animal models. This lack of sedative activity of rilmenidine is rather attributed to an unknown central component of rilmenidine, which counteracts sedation, than to differences in selectivity or affinity-intrinsic activity at the level of α 2 adrenoceptors. The central process counteracting sedation needs to be clarified.