OBJECTIVE This study assessed the mechanism(s) of the decrease in upright blood pressure in patients with supine hypertension by using the tilt test and a hemodynamic approach. BACKGROUND Orthostatic hypotension in patients with supine hypertension creates a pathophysiologic and therapeutic dilemma. METHODS We studied 28 consecutive patients with history of orthostatic intolerance amounting to recurrent syncope in 13 of them (15 men, 13 women; mean [SD] age 65 +/- 11 years). They all had supine hypertension (systolic blood pressure > 160 mm Hg) and orthostatic hypotension (found to be a decrease in systolic blood pressure > 30 mm Hg during tilt test). Cardiac output, cardiopulmonary volume and systemic resistance were assessed by radionuclide first-pass technique (technetium-99m red blood cell tagging). Total blood volume was determined by radioiodinated serum albumin, and the ratio of cardiopulmonary to total blood volume was used as an index of venous capacitance. RESULTS Twenty-one patients had accentuated venous pooling defined as a tilt-induced decrease in cardiopulmonary volume/total blood volume ratio > 15% from baseline or a supine ratio < 14% (normal 16% to 18%), or both. Seven of the 28 patients had autonomic insufficiency; 6 of the 7 also had venous pooling; 1 patient had autonomic insufficiency only. Neither clinical history nor changes during tilt differentiated the subgroups. Plasma catecholamine levels increased during head-up tilt in all subgroups, and differences in their increase were not significant between patients with venous pooling and those with autonomic insufficiency. However, radionuclide hemodynamic variables revealed that patients with venous pooling compensated for the decrease in stroke volume by increasing peripheral resistance, whereas patients with autonomic dysfunction did not. CONCLUSIONS Orthostatic hypotension in patients with supine hypertension may have multiple etiologies. Hemodynamic assessment with determination of cardiopulmonary volume and systemic vascular resistance differentiated between venous pooling and autonomic insufficiency in these patients; head-up tilt and plasma catecholamine levels did not. These findings may have important therapeutic implications.