DG-5128 (2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate) at concentrations up to 10 microM inhibited [3H]clonidine binding more effectively than it did [3H]prazosin binding in rat cerebral cortex membranes. The mode of inhibition was homogeneous and consistent with the law of simple mass action. DG-5128 exhibited a 7.4 times higher affinity (pKi = 6.28) toward alpha 2-adrenoceptors than alpha 1-adrenoceptors. The results indicate that DG-5128 is a preferential alpha 2-antagonist.