To test the hypothesis that age-related increases in arterial pressure alter the cardiovascular response to physiologic stress, 9 healthy elderly volunteers (74 ± 2 years) and 7 young subjects (27 ± 3 years) were subjected to a standard 60 ° upright tilt. Cardiac volumes were measured with patients in the supine position and 5 minutes after they assumed an upright posture using radionuclide ventriculography, while heart rate, blood pressure and forearm cutaneous flow were recorded continuously and simultaneously. Only the expected age-related increase in mean arterial pressure (young subjects, 79 ± 1 mm Hg; elderly subjects, 99 ± 3 mm Hg; p < 0.001) distinguished the 2 groups at baseline. However, during upright tilt, elderly subjects had significant decreases in stroke volume (supine [108 ± 9 ml]vs upright [78 ± 9 ml]; p < 0.01) and cardiac index (supine [3.4 ± 0.2 liters/min/ m2] vs upright [2.8 ± 0.2 liters/min/m2]; p < 0.05) because of an inability to reduce end-systolic volume (supine, 44 ± 6 ml; upright, 51 ± 7 ml); however, mean arterial pressure was maintained through an increase in peripheral resistance. In contrast, the young relied solely on cardiac adaptations to postural stress by decreasing end-systolic volume (supine, 62 ± 5 ml; upright, 39 ± 5 ml; p < 0.01) and increasing heart rate (57 ± 2 min-1 to 71 ± 3 min-1 p < 0.01), whereby cardiac output and mean arterial pressure were maintained during tilt. When oral diltiazem was administered, the elderly demonstrated a significant reduction in mean arterial pressure and external stroke work and were subsequently able to decrease end-systolic volume during postural stress. Thus, age-related increases in mean arterial pressure, even within a range considered to be normal, contribute to increased afterload and alter the hemodynamic response to passive postural stress.