Severe increases in blood pressure (BP) are associated with a segmental pattern of constriction and dilatation in small arteries and arterioles, but the pathogenesis is poorly understood. We showed that the isolated, perfused rabbit ear artery typically develops segmental constriction and dilatation when intraluminal pressure is > 160–180 mm Hg during field stimulation of perivascular nerves (>6 Hz) or extra- or intraluminal infusions of norepinephrine (NE > 10-7M) or phenylephrine (PE) (>5 x 10-7M). Light, transmission, and scanning electron microscopy showed that the dilated vessel segments initially show endothelial injury with no smooth muscle lesions. After repeated or prolonged exposure to high intraluminal pressure, dilated segments manifest extensive and severe endothelial and smooth muscle damage. Dilated regions also became abnormally permeable to tracer particles (ferritin). Constricted segments did not show evidence of endothelial or smooth muscle injury or hyperpermeability. These changes, i.e., segmental vaso-constriction/dilatation, hyperpermeability, and vessel wall damage localized to dilated segments, are comparable to those that occur in small arteries and arterioles during severe hypertension. We discuss the potential usefulness of the isolated ear artery as a model for studying the pathogenesis and morphology of segmental vasocon-striction/dilatation.