The agonist selectivities of central (medullary) and peripheral (vascular) alpha-adrenoceptors were compared in order to investigate a possible similarity among these two alpha-adrenoceptor populations. Linear regression equations were derived between the alpha-adrenergic potencies, mediated by these two types of alpha-adrenoceptors for 21 structurally dissimilar alpha-adrenoceptor agonists. Hypotensive potency after intravenous administration to anesthetized, normotensive rats was determined as a measure of central alpha-adrenergic activity and expressed as pC25, obtained from log dose-response curves. Peripheral alpha-adrenergic potency was quantified by means of the hypertensive effect elicited in pithed, normotensive rats after intravenous injections, yielding pC60 as the biological variable. A most significant linear relationship was generated between central hypotensive activity (pC25) and peripheral hypertensive potency (pC60), provided that log P' (octanol/buffer; pH 7.4, 37 degrees C) was included into the regression in a parabolic form. This result indicates that the central (medullary) alpha-adrenoceptors and the peripheral (vascular) alpha-adrenoceptor sites, which are excited by the drugs in question, make identical demands upon their agonists. The difference in accessibility to these peripheral and central alpha-adrenoceptor populations is adequately accounted for by a parabolic description in log P'. The apparent contradiction of this finding with the suggestion that central, hypotensive alpha-adrenoceptors are of the alpha 2 type and peripheral, vascular alpha-adrenoceptors belong to the alpha 1 subpopulation is discussed. The recent identification of an additional subclass of postsynaptic, vascular alpha 2-adrenoceptors and the lack of pronounced differential stimulating activity of the agonists at peripheral alpha-adrenoceptors may explain the present findings and clarify the paradox.