Postprandial hypotension occurs commonly in patients with autonomic failure and may be due to attenuation of the normal sympathetic nervous system activation in response to meal ingestion. In a randomized, double-blind, placebo-controlled study, we investigated the therapeutic effect of the norepinephrine precursor 3,4-DL-threo-dihydroxyphenylserine (DL-DOPS) on this condition. We measured blood pressure, heart rate, forearm vascular resistance, and plasma DL-DOPS and norepinephrine in 11 patients with autonomic failure. DL-DOPS attenuated the postprandial fall in blood pressure. This was associated with an increase in plasma norepinephrine and forearm vascular resistance. DL-DOPS therapy did not change the postprandial increase in heart rate. There was a trend toward increased supine hypertension associated with DL-DOPS treatment. This study shows that DL-DOPS is a promising treatment for postprandial hypotension and provides support for the hypothesis that postprandial hypotension is, at least in part, due to decreased activation of the sympathetic nervous system.