Cardiovascular effects of an essential oil from the aerial parts of Mentha x villosa (OEMV) were tested in rats using a combined in vivo and in vitro approach. In non-anesthetized normotensive rats, OEMV (1, 5, 10, 20, 30mgkg - 1 body wt., i.v.) induced a significant and dose-dependent hypotension (-3+/-1.8%; -6+/-0.7%; -40+/-6.7%; -58+/-3.8%; -57+/-2.1%, respectively) associated with decreases in heart rate (-1+/-0.3%; -9+/-0.9%; -17+/-3.2%; -72+/-3.1%; -82+/-1.4%, respectively). The hypotensive and bradycardic responses evoked by OEMV were attenuated and blocked by pre-treatment of the animals with atropine (2mgkg - 1 body wt., i.v.). In isolated rat atrial preparations, OEMV (10, 100, 300, 500μgml - 1 ) produced concentration-related negative chronotropic and inotropic effects (IC 5 0 value=229+/-17 and 120+/-13μgml - 1 , respectively). In isolated rat aortic rings, increasing concentrations of OEMV (10, 100, 300, 500μgml - 1 ) were able to antagonize the effects of phenylephrine (1μM), prostaglandin F 2 α (10μM) and KCl (80mM)-induced contractions (IC 5 0 value=255+/-9, 174+/-4 and 165+/-14μgml - 1 , respectively). The vasorelaxant activity induced by OEMV was attenuated significantly by either endothelium removal (IC 5 0 value=304+/-9μgml - 1 ), N G -nitro l-arginine methyl ester (l-NAME) 100μM (IC 5 0 value=359+/-18μgml - 1 ), l-NAME 300μM (IC 5 0 value=488+/-20μgml - 1 ) or indomethacin 10μM (IC 5 0 value=334+/-18μgml - 1 ). However, it was not affected by atropine 1μM (IC 5 0 value=247+/-12μgml - 1 ). Furthermore, the hypotensive response induced by OEMV was attenuated significantly after nitric oxide (NO) synthase blockade (l-NAME, 20mgkg - 1 body wt., i.v.), while bradycardia was not altered. The results suggest that the hypotensive effect induced by OEMV is probably due to its direct cardiodepressant action and peripheral vasodilation, which can be attributed to both endothelium-dependent (via EDRFs, at least NO and prostacyclin) and endothelium-independent mechanisms (such as Ca 2 + channel blockade).