The effects of various vasodilators on isolated helical strips of rat portal vein and mesenteric artery were examined. Dilazep, ibudilast, nifedipine, verapamil and papaverine relaxed the KCl- and norepinephrine-induced contractions of the portal vein to a greater extent than they relaxed those of mesenteric artery. Dibutyryl cyclic AMP and NKH477 did not show any significant difference in terms of the concentrations that produced 50% inhibition (IC50) of the KCl-induced contraction of the portal vein and mesenteric artery. The relaxant effects of nitroprusside and isosorbide dinitrate on the KCl- and norepinephrine-induced contractions of the portal vein were less potent than their effects on contractions of the mesenteric artery. The agents that inhibited the contractions of the portal vein more potently than those of the mesenteric artery were associated with parallel shifts to the right of the concentration-response curves for CaCl2 in both preparations. These results suggest that drugs with a Ca2+ channel blocking action may be preferable to those that cause a decrease in portal pressure for treatment of portal hypertension.