The influence of tris(hydroxymethyl)-aminomethane (Tris) on the spontaneous mechanical activity (SMA) and agonist-induced contractile responses of rat portal vein and aorta was investigated. Tris, in a concentration-dependent manner (5, 10, and 30 mM), significantly increased frequency and attenuated amplitude of SMA in portal vein. Tris, in all concentrations, abolished spontaneous activity of aorta. Tris (5 mM) attenuated epinephrine-, angiotensin-, and potassium-induced contractile responses in portal vein and in aorta: the vein responses exhibited the greater sensitivity to Tris inhibition. In the presence of Tris, agonist dose-response curves were shifted to the right, concomitant with a reduction in maximum tension in portal vein. In contrast, in aorta, only a rightward shift of the dose-response curves was observed, withour any change in maximum tensions in the presence of Tri. Tris (5 mM) depressed contractions induced by calcium in potassium-depolarized aortic and venous smooth muscle. These results suggest that Tris may interfere with the binding, translocation, and utilization of calcium ions at or beyond the membrane in venous smooth muscle and at the membrane in aortic smooth muscle.