The time course and mechanism of systemic hypertension associated with infrarenal aortic cross-clamping were investigated in 31 chloralose-anesthetized dogs after ligating the tail artery, the paired infrarenal lumbar arteries, and the circumflex iliac arteries bilaterally. Cardiac output, renal blood flow, and suprarenal and infrarenal mean arterial blood pressure were continuously monitored. Infrarenal aortic clamping (90 min) in the standard group ( n = 6) consistently decreased infrarenal blood pressure from 90 ± 6 to 13 ± 1 mm Hg within 1 min, while suprarenal blood pressure gradually increased over 20-30 min from 88 ± 7 to 144 ± 8 mm Hg, where it remained until declamp. The SHAM group (identical operation and instrumentation, without aortic clamping) ( n = 5) showed no statistically significant changes. After 90 min of clamp total peripheral and renal resistance nearly doubled but no statistically significant changes in cardiac output, heart rate, central venous pressure, renal blood flow, renin, or glomerular filtration rate were detected. Upon declamping, pressures returned to control levels within 20 min. Groups with bilateral nephrectomy ( n = 9) or unilateral iliac artery clamping ( n = 7) produced similar time courses and patterns of hemodynamic change. Ablation of afferent nerves from the left hind limb ( n = 4) eliminated the hypertension produced by left iliac artery clamping. The substantial delay (20-30 min) to the onset and full development of suprarenal hypertension, with near immediate infrarenal hypotension, is not consistent with a direct mechanical impedance effect. Hypertension in the presence of a bilateral nephrectomy or unilateral iliac artery clamping combined with its full reversal by nerve section strongly suggests that this is a reflex hypertension. This reflex mechanism of hypertension development has implications for intra- or perioperative events associated with hypertension management.