Mechanical activity of the isolated portal vein and thoracic aorta of the guinea-pig was recorded and the effects of verapamil and D 600 (methoxy-verapamü) on the dose-response curves to noradrenaline were measured. Extracellular electrical activity in portal vein was also sometimes recorded. Two calcium activation mechanisms could be differentiated: a ‘spike activation mechanism’ (SAM) inhibited by verapamil and D 600, and a ‘spike-free activation mechanism’ (SFAM) resistant to these antagonists in their specific concentration range (up to 10<sup>–5</sup> mol/l). In portal vein, both mechanisms were similarly dependent on extracellular calcium, indicating a D 600-resistant system for transmembrane calcium fluxes. The response of portal vein to increased potassium concentration was also tested. Species differences and differences in the specificity of various calcium antagonistic drugs complicate the picture of calcium antagonism in vascular smooth muscle.