Ten patients affected by essential moderate or severe hypertension were given five sequential treatments, each for three weeks: 1) placebo, 2) chlorthalidone (Cl) 100 mg daily, 3) Cl 50 mg + oxprenolol slow release (Ox) 160 mg daily, 4) Ox 160 mg and 5) Ox 320 mg daily. Four subjects poor responders (DPB greater than or equal to 110 mmHg) received a later administration of Ox 160 + Cl 50 + hydrallazine (Hydr) 25-100 mg daily. Both groups of patients showed the greatest antihypertensive action with Ox 160 + Cl 50 mg daily. Oxprenolol induced a similar hypotensive effectiveness at 160, as well as 320 mg/day. Relationship between plasma renin activity (PRA) values and antihypertensive response to each treatment takes the following conclusions: 1) Basal PRA levels cannot be a guide for preferential choice of diuretic or betablocking therapy. 2) It is likely that renin activated by Cl and Hydr partially blunts their hypotensive activity. On the contrary, essential hypertension with normal or low PRA does not seem depending on angiogensinogenic factors. 3) Oxprenolol remarkably inhibits the overreninism induced by chlorthalidone and hydrallazine, in such way increasing their antihypertensive action. 4) In the management of essential moderate or severe hypertension is preferable to employ a mild dosage of betablockers and diuretics, rather than use higher doses of a single agent.