Objective: In this study, we have examined the possibility that there is altered vascular reactivity due to the direct interaction between parasitized erythrocytes and vascular endothelial cells. Method: Ring preparations of rat aorta were studied using standard in vitro techniques, the rings were mounted in 20 ml organ baths containing PSS under an initial load of 1g, maintained at 37°C at pH 7.4 and isometric contractions were recorded electronically. Rings were allowed 90 minutes to equilibrate before the commencement of the various protocols: * Dose responses to phenylephrine (PE) and other vasoactive agents (high-K+) * Acetylcholine (Ach) – induced relaxation in phenylephrine-contracted rings (pre-contraction was induced by EC70 concentration of phenylephrine) * Ach-induced relaxation in PE-precontracted, endothelium-denuded rings * Also, relaxation responses to acetylcholine was investigated through application of a single (EC70) concentration of acetylcholine in rings exposed to blood with varying concentrations and dilutions of parasitized blood and varying durations of exposure. Results: Incubation with parasitized blood resulted in a significant increase in maximum contractile response to phenylephrine in the rat aortic rings (p < 0.05) but no effect to the base line. Analysis of the whole dose-response curve (using paired t-test) showed a significant left-ward shift following the addition of parasitized blood (p < 0.05), EC70 (M) values increasing from 7 x 10-7 to 5 x 10-6M. Following exposure to parasitized blood, the magnitude of Ach-induced relaxation responses reduced significantly from 73 ± 3.6 to 24.75 ± 7.25% in rat aortic rings (p < 0.05). Ach relaxations were significantly enhanced (p < 0.05) at 5-minute exposure; however at longer durations, Ach-relaxations were variable and inconsistent. The lesser the dilution, due to increased volume of parasitized blood, the lesser the relaxation response. Following endothelium removal, there was a marked impairment in endotheliumdependent relaxation responses to ACh in both the control and incubated vessels. Exposure to parasitized blood did not significantly alter contractile responses induced by potassium depolarization. Conclusions: This gives evidence in support of an endothelium-dependent action of malaria parasites as vascular effects of malaria parasites are mediated, at least in part, via endothelium-dependent mechanism(s).