The effects of bepridil and its quaternary analogue, methylated bepridil, were studied on femoral arterial strips from spontaneously hypertensive rats (SHR). Methylated bepridil relaxed precontracted strips more rapidly than did bepridil, but bepridil was a more potent vasorelaxant. Both drugs non-competitively inhibited arterial contraction evoked by voltage-dependent or alpha-adrenoceptor-operated Ca2+ influx with bepridil being more potent than methylated bepridil. In the absence of extracellular Ca2+, the contractile responses of Wistar-Kyoto rats (WKY) and SHR arteries to norepinephrine and caffeine were reduced similarly by methylated bepridil and bepridil. It is suggested that the effects of bepridil involve both extracellular and intracellular actions. The altered sensitivity of the contraction mechanism with norepinephrine-releasable Ca2+ to the Ca2+ antagonist may be due to an abnormality in the intracellular vasocontraction process distal to Ca2+ release from storage sites of the SHR blood vessels.