In chronic autonomic failure, food ingestion causes a profound and rapid fall in supine blood pressure and aggravates postural hypotension. Food volume and caloric load are important determinants of gastric emptying and postprandial splanchnic hyperaemia, which appears to be a major contributor to hypotension. We therefore compared the cardiovascular effects of three large meals with six small meals providing an identical daily caloric intake, in seven subjects with primary autonomic failure. Daytime ambulatory blood pressure (BP) was measured by Spacelabs 90207 every 30 min with additional recordings while lying, sitting and standing, 30 min after each meal. Systolic and diastolic BP were lower in all three positions after large meals; systolic 131 versus 151 mmHg (large versus small), p = 0.005, 109 versus 124 mmHg, 89 versus 103 mmHg and diastolic 76 versus 90 mmHg, p = 0.02, 66 versus 78 mmHg, p = 0.07 and 50 versus 66 mmHg, p = 0.06 for lying, sitting and standing, respectively. Between meals, BP fell to lower levels with large meals, 88 (20) mmHg versus 104 (19) mmHg, p = 0.002 and 48 (13) mmHg versus 63 (13), p = 0.0001 mmHg for systolic and diastolic pressure respectively. Five subjects had more symptoms of postural dizziness after large meals. In primary autonomic failure, smaller and more frequent meals reduce postprandial hypotension and diminish postural symptoms post-meal. This is likely to be a useful non-pharmacological method in the management of postprandial hypotension.