48 patients with normal-renin essential hypertension were treated with prazosin alone or in combination with oxprenolol. 1 h after a single dose of 2 mg prazosin tachycardia and a decrease in blood pressure developed. Renin activity in the peripheral plasma (PRA) increased from 1.04 ± 0.15 to 2.64 ± 0.20 ng AgT/ml/h. A 3-day treatment with 2 mg t.i.d. prazosin of 11 patients caused no further decrease in blood pressure, while PRA returned to the baseline level. Treatment for 3 days with 2 mg prazosin t.i.d. and 40 mg oxprenolol t.i.d. of 37 patients further decreased blood pressure as well as PRA. The increase in PRA after a single dose of prazosin could be related to the enhanced sympathetic activity. The decreased PRA after prazosin + oxprenolol therapy may be one of the factors responsible for the greater antihypertensive response to the combined therapy.