1. The anti-hypertensive actions of timolol and hydrochlorothiazide were analysed in a double-blind 2 × 2 factorial trial in twenty patients with essential hypertension. Each patient went through four phases of 8 weeks in randomized order, receiving timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and placebo.
2. Supine mean arterial pressure fell from 119 mmHg in the placebo phase, to 110 mmHg during the thiazide phase, 106 mmHg during the timolol phase, and to 101 mmHg during the combined timolol plus hydrochlorothiazide phase.
3. Factorial analysis revealed that the hypotensive actions of the β-receptor-blocking drug and the diuretic were additive, without any synergism or antagonism.
4. Plasma renin activity measured in ng 3 h—1 ml—1 rose from 502 in the placebo phase to 9·54 in the diuretic phase, but fell to 1·79 in the β-receptor blockade. It was unchanged in the combined therapy phase, despite the greater drop in blood pressure. These results suggest that the fall in plasma renin activity during β-receptor blockade is of little importance in the hypotensive action of β-receptor-blocking drugs.