1. In four patients, whose hypertension was not controlled (supine blood pressure > 150–90 mmHg) by addition of 5 mg/day of prazosin to previous treatment (diuretics and β-blockers), clonidine (150–450 μg/day) led to control of hypertension in three cases.
2. In ten patients whose hypertension was not controlled by a treatment including clonidine (300–450 μg/day), the progressive addition of prazosin to a maximal dose of 4–22.5 mg/day led to control of hypertension in nine cases (mean supine blood pressure decreased from 174–102 to 144–88 mmHg).
3. In 13 hospitalized patients, clonidine was abruptly interrupted whereas prazosin was continued. Mean blood pressure (± sem) rose from 145 ± 1/85 ± 2 to 169 ± 7/104 ± 5 mmHg 48 h after clonidine withdrawal whereas plasma noradrenaline and adrenaline rose from 328 to 758 pg/ml and from 75 to 137 pg/ml. No subjective symptoms were noted. There was a negative correlation between blood pressure increase and the dose of prazosin.
4. It is concluded that (a) there is no antagonism between clonidine and prazosin in their antihypertensive action in man when used at usual clinical doses, (b) a protective effect of prazosin against an eventual clonidine withdrawal syndrome is suggested by the negative correlation between blood pressure increase and the dose of prazosin.