1 A single 500 micrograms oral dose of prazosin was associated with significant suppression of sympathetically mediated venoconstriction, as measured by the venous reflex response in six healthy volunteers. 2 The impaired venous reflex response consistently preceded orthostatic hypotension and tachycardia, which were associated with faintness and other unpleasant symptoms. 3 The plasma prazosin concentration, which was measured by a sensitive, specific h.p.l.c. assay, varied appreciably both between and within individual subjects. 4 There was no precise relationship between the plasma prazosin concentration and the symptomatic haemodynamic effects observed. 5 It was concluded that reduced venous return to the heart, due to significant suppression of sympathetically mediated venoconstriction by small initial oral dosage of prazosin, contributes to the pathophysiology of the orthostatic hypotension and faintness, described as the ‘first‐dose phenomenon’.