Minoxidil, an orally effective vasodilator, was successful in lowering blood pressure in 10 patients with systemic diseases complicated by hypertension refractory to medical management. Follow-up was for periods up to 58 months. In patients not requiring dialysis prior to therapy, renal function was preserved, and in patients on dialysis, bilateral nephrectomy was avoided. Although sodium retention and reflex tachycardia were common, they were managed by beta-adrenergic blockade with propranolol and diuresis with furosemide. Results did not differ qualitatively or quantitatively from those achieved in 31 refractory hypertensives without systemic illness. Pharmacologic studies performed on hemodialysis in a patient with polyarteritis revealed a dialysis clearance of 14C-labeled minoxidil of 48 ml/min. Venous minoxidil concentrations decreased by 32% across six single dialysis treatments. Nineteen percent of the administered dose was recovered in the feces, an increased fraction compared to normal subjects.