The mechanisms of the vascular effects of somatostatin (ST) are not well known. This study compares the direct effects of ST in different vascular regions and species. Isolated perfused segments of the cat superior mesenteric artery in vitro did not exhibit a vascular response in the resting state, however, ST-induced vasodilatation was observed with norepinephrine preconstriction. In contrast, ST only slightly dilated superior mesenteric vein segments. In the artery, NG-nitro-L-arginine inhibited both ST and endothelium-dependent nitric oxide (NO) mediated response. No regular dose-response curves were found when ST was applied on the large mesenteric artery in the cat, but rings of small mesenteric artery from both cats and dogs exhibited dose-dependent relaxations. These effects were also NO-dependenL Local application of ST on the rat saphenous artery in situ elicited NO-mediated dose-dependent vasodilatation. However, ST constricted rat saphenous veins in the case of either adventitial or intraluminal application. It is concluded that ST exerts different actions on the arterial and the venous vessel wall. The major response in arteries is endothelium-mediated vasodilatation seen in various species and vascular beds. Large and small arteries respond differently to ST but these differences require further elucidation.