The effect of food ingestion of supine blood pressure was assessed during 25 studies in 10 subjects with autonomic dysfunction. Profound decreases in both systolic and diastolic pressure occurred. The mean (+/- standard error of the mean) maximal reduction in systolic blood pressure for the entire group was 49 +/- 6 mm Hg (range 22 to 98). The response also occurred in hypertensive subject after surgical sympathectomy and during alpha adrenergic blockade and hence appears to be a general phenomenon when sympathetic vasoconstrictor function is impaired. The depressor effect of food ingestion was enhanced by propranolol, attenuated by indomethacin and unaffected by diphenhydramine and cimetidine. The phenomenon is thus not explained by histamine release, and can only partly be accounted for by release of arachidonic acid metabolites. Evidence that insulin may play a role in the phenomenon is discussed. Manipulation of diet may prove to be an important adjunct in the management of patients with autonomic dysfunction.