Renovascular hypertension alters endothelial-dependent mechanisms to affect the response of small arterioles in skeletal muscle to sepsis. Small arteriole responses to sepsis differ between skeletal muscle and small intestine in normotensives. Our study now shows that renovascular (1K1C) hypertension alters small arteriole responses in the small intestine to Escherichia coli sepsis. Large arterioles (A1, A2) constricted by 10–20% in the small intestine of both normotensive and hypertensive rats during both high and low cardiac output sepsis. Small arterioles (premucosal A3and preserosal A4) constricted during high cardiac output sepsis in normotensive but not hypertensive rats. Small A3and A4arterioles dilated (20–40%) during low cardiac output sepsis in hypertensives; but only A3and not A4arterioles dilated in normotensives during low cardiac output sepsis. Acetylcholine, which releases endothelial-derived relaxing factor in skeletal muscle, dilated both premucosal A3and preserosal A4in both normotensive and hypertensive rats. Thus, hypertension alters small arteriole responses to sepsis in both skeletal muscle and small intestine, but apparently by different mechanisms.