Intraluminal pressure may affect vascular contractility in both normotension and hypertension. To test this hypothesis, we studied mesenteric resistance arteries from normotensive humans as well as normotensive (WKY) and spontaneously hypertensive (SHR) rats (internal diameter 214 ± 27, 201 ± 6, and 172 ± 6 μm, mean ± SEM at 10 mm Hg). Vessels were mounted on glass cannulas and perfused in organ chambers filled with buffer solution at intraluminal pressures of 10 to 120 mm Hg; vasomotion was measured using a video dimension analyzer. Under baseline conditions (10 mm Hg), wall thickness was 36 ± 4 μm in humans, 32 ± 4 μm in WKY, and 47 ± 2 μm in SHR (P < .001). With increasing pressure, the diameter of human vessels increased up to 25 mm Hg and remained constant at higher pressures. In contrast, resistance arteries of normotensive and hypertensive rats exhibited an almost linear increase in diameter over the whole pressure range. In SHR, the pressure-diameter relationship was much flatter than that of WKY, indicating reduced compliance. In human arteries, the contraction to KCl was maximal at 25 mm Hg and averaged 40 ± 6%. Both above and below 25 mm Hg, the response declined to a minimum of 17 ± 2% at 120 mm Hg (P < .01). Similar results were obtained in WKY rats. In contrast, the contractile response in SHR remained maximal over the entire pressure range studied (65 ± 5%). Thus, intraluminal pressure profoundly affects vascular reactivity of resistance arteries; low pressure augments and high pressure reduces the contractile response in normotensive human and rat resistance arteries, whereas this pressure-dependent modulation of vascular reactivity is lost in the SHR. Am J Hypertens 1992;5:542-54