After space-flights of less than ten days, orthostatic hypotension upon reentry is characterized by plasma volume depletion that may lead to activation of the Bezold-Jarisch reflex which is also considered to be the mechanism of vasovagal (neurocardiogenic) syncope. For space-flight of longer duration, loss of cardiovascular reflex control may take precedence over volume depletion and thus may have similarities to the orthostatic hypotension seen in patients with autonomic failure secondary to basal ganglial disease and peripheral neuropathies. Midodrine is an alpha-one agonist that produces arterial and venous constriction and leads to a decrease in heart rate by baroreceptor reflexes. The efficacy of Midodrine in successfully treating orthostatic hypotension secondary to autonomic failure has been shown in clinical trials. Midodrine's ability to vasoconstrict without increasing heart rate suggests that it might be a useful treatment for vasovagal syncope since stimulation of the Bezold-Jarisch reflex would be less likely. For post-space flight orthostatic hypotension, midodrine may be a useful adjunctive treatment to the measures currently being used.