Aging is associated with alterations in cardiovascular homeostasis that impair adaptation to common hypotensive stresses. Postprandial blood pressure (BP) reduction has been described in elderly subjects, but its clinical significance and pathophysiologic mechanisms are unknown. We have identified 8 elderly patients with meal-related syncope and large postprandial BP declines. To evaluate the role of sympathetic nervous system activity and insulin in the development of postprandial BP reduction, mean arterial BP, heart rate, plasma catecholamine and insulin responses to a high carbohydrate meal in these 8 syncope patients were compared with those of 7 young and 12 old nonsyncopal controls. By 60 minutes after the meal, mean arterial BP declined an average of 26 mm Hg (p = 0.001) in old syncope patients, in contrast to a decline of 9 mm Hg (p = 0.1) in elderly controls and no change in young controls. Young and old controls had significant, sustained increases in heart rate or plasma norepinephrine levels, or both, throughout the 90-minute postprandial period. However, elderly syncope patients had no significant change in heart rate and only an initial increase but subsequent sustained decrease in plasma norepinephrine levels that paralleled the marked mean arterial BP reduction. Insulin and glucose responses were not significantly correlated with mean arterial BP reduction. These findings demonstrate that compared with old and young controls, elderly patients with meal-related syncope have marked sustained declines in postprandial mean arterial BP associated with a failure to maintain compensatory norepinephrine levels and cardioacceleratory responses.