The dependence of Ca2+ for different modes of activation has been investigated in the rat portal vein in vitro by evaluating the effects of substituting Sr2+ for Ca2+ in the extracellular fluid. For the spontaneous contractile activity as well as for contractures induced by depolarizing (high-K+) solution Sr2+ can to a large extent replace Ca2+. Sr2+ is however a poor Ca2+-substitute for the contractile response induced by alpha-stimulation (noradrenaline). The inhibition of spontaneous contractions by beta-stimulation (isoprenaline) is markedly less pronounced in Sr2+ solutions. Available data in the literature suggest that agonist interaction with alpha-receptors, in contrast to beta-receptors, is Ca2+ independent. Our results thus suggest that there exists a Ca2+ specific step between the alpha-receptor agonist occupancy and membrane excitation.