Abstract-The role of T-type Ca 2ϩ channels for cardiovascular physiology, in particular blood pressure regulation, is controversial. Selective blockade of T-type Ca 2ϩ channels in resistance arteries has been proposed to explain the effect of the antihypertensive drug mibefradil. In the present study, we used a third generation, time-and tissue-specific conditional knockout model of the L-type Ca 2ϩ channel Ca v 1.2 (Ca v 1.2 SMAKO mice) to genetically dissect the effects of mibefradil on T-and L-type Ca 2ϩ channels. Myogenic tone and phenylephrine-induced contraction in hindlimb perfusion experiments were sensitive to mibefradil in control mice, whereas the drug showed no effect in Ca v 1.2-deficient animals. Mean arterial blood pressure in awake, freely moving control mice was reduced by 38Ϯ2.5 mm Hg at a dose of 1.25 mg/kg bodyweight mibefradil, but not changed in