1 The hypotensive effect of single daily dosing with 80 mg penbutolol was compared to 100 mg hydrochlorothiazide and placebo in a double-blind cross-over controlled trial with daily home measurements in ten hypertensive patients. 2 Penbutolol, 80 mg once a day, reduced significantly the supine and standing blood pressure. 3 This hypotensive effect was more potent than hydrochlorothiazide 100 mg particularly in the evening. 4 The hypotensive effect remained for 24 h as shown by the evening (14 h after dose) and morning (24 h after dose) blood pressure readings. 5 No relevant subjective or physical side effects were recorded. There was no significant change nor individual noticeable variation in biochemical data during penbutolol treatment. However, during hydrochlorothiazide treatment, the expected electrolyte changes were observed (symptom-free hypokalemia and hyperuricemia). 6 Penbutolol serum concentration showed no cumulation after one month of treatment. 7 Sudden withdrawal of penbutolol after 1 month of therapy resulted in a slow return to baseline blood pressures over a 2-week period without rebound.