Neurogenic orthostatic hypotension is a severely disabling condition due to deficient peripheral vasoconstrictor tone in response to the upright position and is characterized by a decrease in blood pressure upon standing associated with symptoms of lightheadedness, dizziness, visual "white-out", weakness, lack of energy, near syncope or even syncope. Previous pharmacologic treatment of neurogenic orthostatic hypotension has been problematic. Midodrine, a new specific alpha-1-agonist has been shown to produce arteriolar constriction and decrease in venous pooling via a constriction of venous capacitance vessels. Therefore, a recent multicenter study evaluated the safety and efficacy of midodrine therapy in 97 patients with neurogenic orthostatic hypotension due to various etiologies: Shy Drager syndrome (No. 18); Bradbury Eggleston syndrome (idiopathic orthostatic hypotension) (No. 20); diabetic autonomic neuropathy (No. 27); Parkinson's disease (No. 22); and miscellaneous (No. 10). Following one week of placebo therapy, the patients were randomized into 4 groups for a 4 week period of time; placebo, 2.5 mg, 5 mg, or 10 mg three times daily. The BE/SDS subgroup demonstrated a 27 +/- 8% (22 mmHg) increase in standing systolic blood pressure for the 10 mg dose. Diabetics achieved a significant increase at 5 mg. Similar increases were observed for the entire group on the 10 mg dose (p < 0.001). Symptoms or fainting, blurred vision, improved energy level, standing time, and depressed feelings were also significantly improved even at lower doses (p < 0.05 or less). Side effects were mild. Therefore, midodrine is an effective and safe agent for the treatment of neurogenic orthostatic hypotension.