Using [3H]-WB 4101 binding assay in rat cerebral cortex membranes, effects of 18 mexiletine derivatives on alpha 1-adrenoceptors were studied in order to find new antihypertensive alpha 1 receptor blocking agents. The results showed that 6 of them showed significant affinities to alpha 1-adrenoceptors in rat cerebral cortex membranes. Some structure-activity relationship were found, among them only the compounds with chiral carbon showed high affinity to alpha 1-adrenoceptor. The affinity of compound M-85001 (pKi = 6.51) was shown to be higher than that of tolazoline. In the rat anococcygeal muscle, compound M-85001 competitively antagonized phenylephrine-induced contraction with pA2 value of 6.86 which is similar to its pKi value in the binding assay. These findings may be of significance in the search for novel class of alpha 1 receptor antagonists.