We determined the pressor effect of phenylpropanolamine hydrochloride, a widely used sympathomimetic agent, in 14 patients with autonomic failure and orthostatic hypotension. Blood pressure was monitored every five minutes in the sitting position with an automated device. Oral administration of 25 mg of phenylpropanolamine hydrochloride in nine patients produced significant increases in systolic (32 mm Hg), diastolic (15 mm Hg), and mean (21 mm Hg) blood pressures. The pressor effect appeared within the first 60 minutes and was still present at 105 minutes. There was no change in heart rate. Blood pressure was also significantly raised by administration of 12.5 mg of oral phenylpropanolamine hydrochloride in five additional patients. We conclude that administration of 25 mg of phenylpropanolamine hydrochloride elicits a potent pressor response in patients with orthostatic hypotension and that significant hypertension may result.