In this study, we examined the effects of Psidium guajava Linn. leaf aqueous extract (PGE) on isolated, spontaneously-contracting portal veins, as well as on endothelium-intact and endothelium-denuded descending thoracic aortic ring preparations of healthy, normotensive rats. Graded concentrations of PGE (0.25-4.0 mg/ml) caused concentration-dependent, initial brief but significant (P<0.05) rises of the basal tones and amplitudes of pendular, rhythmic contractions, followed by secondary pronounced, longer-lasting and significant (P<0.05-0.001) inhibitions of contractile amplitudes of the isolated portal veins. Relatively low concentrations of PGE (<1.0 mg/ml) always contracted freshly-mounted, naïve, endothelium-intact aortic ring preparations. However, relatively high concentrations of PGE (1.0-4.0 mg/ml) always produced initial brief contractions/augmentations of noradrenaline (NA, 10^-7M)-induced contractions of endothelium-intact and endothelium-denuded aortic ring preparations, followed by secondary, pronounced relaxations of the aortic ring muscles. Moreover, relatively high concentrations of PGE (1.0-4.0 mg/kg) always relaxed NA-induced contractions of the aortic ring preparations in a concentration-related manner. The arterial-relaxing effects of PGE were more pronounced in endothelium-intact aortic rings than in endothelium-denuded aortic ring preparations. The relaxant effects of PGE on endothelium-intact aortic rings were only partially inhibited by N^G-nitro-L-arginine methyl ester (L-NAME, 100 μM), a nitric oxide synthase inhibitor, suggesting that the vasorelaxant effect of PGE on aortic rings is probably mediated via both endothelium-derived relaxing factor (EDRF)-dependent and EDRF-independent mechanisms. Taken together, the findings of this study indicate that PGE possesses a biphasic effect on rat isolated vascular smooth muscles.