The objectives of this study were to determine the hemodynamic and microcirculatory changes that occur during reduced renal mass hypertension in rats. In conscious animals with 75% reduction of total renal mass, mean arterial pressure was initially (4–8 hours) elevated by 15–20 mm Hg during intravenous infusion with isonatremic (145.4 mM) NaCl. Cardiac index was elevated by 15–20%, and total peripheral resistance index was normal or reduced. Cardiac index subsequently returned toward normal, but mean arterial pressure remained elevated (20–40 mm Hg), presumably because of an elevated total peripheral resistance. Cremasteric arterioles were actively constricted (35–50%) in rats with short-term (36 hours), but not chronic (5–6 weeks) reduced renal mass hypertension. Total microvessel density was approximately 15% lower in maximally dilated cremaster muscles of chronically hypertensive rats versus sham-operated controls, which suggests that arterioles are lost during sustained reduced renal mass hypertension. Arteriolar constriction in response to increased superfusate Po2(0% to 5% O2) was 2–4 times greater in rats with both short-term and chronic reduced renal mass hypertension than in normotensive controls, which suggests that oxygen-dependent autoregulatory mechanisms are altered. The hemodynamic and microcirculatory alterations observed in these experiments suggest that classic short-term autoregulatory mechanisms and an enhanced response of arterioles to increased oxygen availability contribute to the elevated total peripheral resistance in short-term reduced renal mass hypertension, whereas structural changes and altered vascular oxygen responses contribute to an elevated microvascular resistance in chronic reduced renal mass hypertension.