The antagonist activity of Wy 26703 at vascular postjunctional alpha-adrenoreceptors was quantified against the methoxamine and B-HT 920-induced increase in diastolic pressure in pithed rats. For Wy 26703 pA2-values (= -log dose antagonist evoking a 2-fold shift for the agonist dose-response curve) of 4.96 and 6.43 are found, respectively, whereas for yohimbine values of 5.72 and 6.83 have been reported. The blocking potencies of Wy 26703 and yohimbine have been compared at cardiac prejunctional alpha 2- adrenoreceptors in rats. pA2-values of 6.84 and 6.97, respectively, resulted for the antagonism against the B-HT 920-induced inhibition of stimulation-induced tachycardia. At central alpha-binding sites Wy 26703 and yohimbine were compared for their ability to displace [3H]-prazosin, [3H]-yohimbine and [3H]-clonidine from their specific binding sites in rat brain homogenates. For both compounds binding data indicated a preferential affinity for cental alpha 2- over central alpha 1-binding sites. Wy 26703 exhibited a greater selectivity for cental alpha 2- as compared with central alpha 2-sites than did yohimbine. It is concluded that Wy 26703 behaves as a potent alpha 2-adrenoreceptor blocking agent, that is more selective than yohimbine for postjunctional and central alpha 2-adrenoreceptors as compared with alpha 1-adrenoreceptors. At cardiac prejunctional alpha 2-adrenoreceptors both blocking drugs appeared to be equipotent.