Aim: The purpose of this study was to determine the mechanism of the directs effects of sevoflurane on human veins in vitro. Methods: Dose-response curves were obtained for cumulative doses of sevoflurane (0.5, 1, 1.5 and 2 MAC) on saphenous vein strips precontracted with 5-hydroxytryptamine ( 5-HT 10-6 mol/L) incubated with either Nω-nitroL-arginine-methyl ester (L-NAME) (10-4 mol/L), indomethacine (10-5 mol/L), glibenclamide (10-6 mol/L) or tetraethylammonium (10-4 mol/L) Results: Preincubation of vein strips with tetraethylammonium (TEA, Ca++-activated K+ channel blocker) did not influence the relaxant responses to sevoflurane (p>0.05). L-NAME, indomethacine and glibenclamide reduced the relaxation response to sevoflurane (p<0.05). Conclusion: Our results demonstrated that sevoflurane produces concentration dependent relaxation in human saphenous vein. The relaxant effects of sevoflurane are probably related with activation of nitric oxide synthase, cyclooxygenase and KATP channels pathways.