Felodipine is a dihydropyridine calcium antagonist that exerts a markedly selective inhibition of the smooth muscle of arterial resistance vessels. In this paper, we report on the effects of felodipine on vascular smooth muscle in vivo and in vitro. Contractions in these effector cells are categorized according to means of activation, membrane events, and sensitivity to felodipine and are discussed in terms of four schematic "activation pathways." Stimulation of aortic smooth muscle by K+ or noradrenaline may be accounted for by separate pathways (I and IV) that might involve potential-operated and receptor-operated Ca2+ channels with high and low sensitivity to calcium antagonists. In the spike-generating vascular smooth muscle of the portal vein, both spontaneous myogenic activity and responses to adrenergic stimuli of physiological intensity are more adequately described in terms of an action potential-mediated pathway (II). This pathway is sensitive to felodipine in nanomolar concentrations irrespective of the primary means of stimulation. Basal tone and adrenergic responses of resistance vessels in vivo show similar sensitivity to felodipine, suggesting that they are also mediated by II or by a closely related pathway (III) involving graded changes in membrane potential rather than in action potentials. The latter activation pathways (II and III) are the ones relevant to the pharmacodynamic effects of felodipine for therapeutic purposes.