The antihypertensive effect of different agents was investigated in patients with essential hypertension both at the clinic and in the ambulatory state using the semi-automatic Remler M2000 blood pressure recorder. In 7 patients treated for 4 weeks with a transdermal therapeutic system delivering clonidine, blood pressures measured at the physician's office were not significantly decreased whereas blood pressures recorded during patients' customary daily activities were markedly reduced. In an additional study performed in double-blind fashion, the blood pressure lowering effect of timolol (10-20 mg/d, n = 14) and of methyldopa (250-500 mg/d, n = 16) were compared. These agents were given for 6 weeks in association with a baseline diuretic therapy of hydrochlorothiazide and amiloride. When assessed at the clinic, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower (p less than 0.05 for the diastolic) in the patients given timolol. These data indicate that blood pressure monitoring outside the clinic makes it possible to detect important differences in the response to antihypertensive therapy even though, based on office blood pressure readings, no significant change occurs. It appears therefore desirable to include ambulatory blood pressure recordings in the design of drug trials.