It has been reported that the first-dose response to prazosin is more common in patients who are salt-depleted or already receiving beta blockers. The relationship between the first-dose blood pressure and plasma renin responses to oral administration of 1 mg prazosin in 13 (seven male, six female) patients with essential hypertension (average blood pressure = 150/100 +/- 5/2 mm Hg) was studied. Eight of 13 patients experienced marked orthostatic decreases in blood pressure associated with nausea and dizziness. The degree of the orthostatic depressor response was inversely correlated with the baseline plasma renin activity (p less than 0.005). This unique sensitivity of low-renin essential hypertension to prazosin may reflect an underlying increased alpha tone and/or an attendant blunted renin reactivity in this form of human essential hypertension.