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Blood pressure readings obtained by the physician in his office and ambulatory blood pressures recorded with the semi-automatic Remler device, were compared during a controlled antihypertensive drug trial. Either timolol or methyldopa was administered in in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure>95 mmHg at the end of a four-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/day) and amiloride (2.5 mg/day). After four weeks of diuretic therapy, timolol (10 mg/day, n=14) or methyldopa (250 mg/day, n=16) were added randomly for six weeks. The dose of all antihypertensive agents was doubled after two weeks of therapy with diuretics combined with timolol (n=7) or methyldopa (n=16) because of the persistence of diastolic blood pressure levels>90 mmHg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower in the patients given timolol (P<0.05 for the diastolic). With both regimens, the blood pressure response measured outside the clinic during usual daily activities could not be predicted from that observed with office blood pressure readings. Furthermore the magnitude of the drug induced blood pressure decrease was more reproducible in time when determined outside the clinic. These data suggest that ambulatory blood pressure monitoring is more precise in evaluating the efficacy of antihypertensive therapy than office blood pressure measurement.