Twenty-nine hypertensive patients refractory to conventional medications were treated continuously with minoxidil, sympathetic suppressants, and diuretics for six months to five years (mean, 30 months). All had evidence of hypertensive end-organ damage before minoxidil therapy. Good blood pressure control was obtained in 21 (72%) of 29 patients when minoxidil was given in dosages up to 40 mg/day. No tolerance was found. In the remaining eight, good control was obtained in three when phenoxybenzamine therapy was added, and in one when clonidine therapy was added. Renal failure requiring hemodialysis developed in five of 29, one had temporary hemiparesis, and one had fatal cerebral hemorrhage. In the remainder, myocardial infarctions and strokes were effectively prevented. Patients receiving minoxidil and propranolol hydrochloride had elevated plasma norepinephrine levels while those receiving clonidine had normal plasma norepinephrine levels.