The antihypertensive effect of a slow-release (SR) clonidine preparation was evaluated in hypertensive patients not confined to bed using a 24-h intraarterial blood pressure monitoring (Oxford) method. The monitoring was carried out during placebo administration and after 7–10 days of daily administration of SR clonidine in a single oral dose (250 or 500 μg). An analysis of all the blood pressure values obtained was performed by computer. The results were as follows: (a) SR clonidine significantly reduced the 24-h systolic and diastolic arterial pressure by 16 and by 10 mm Hg, respectively (mean ± SE). (b) The reduction was well evident throughout the 24-h period, the average decrease in mean arterial pressure observed during the first, second, and third 8-h period after the administration of the drug being 11, 14, and 14 mm Hg, respectively. (c) The blood pressure reduction was similar during the daytime and the nighttime, despite the lower base-line value that occurred in the latter condition. (d) There was no consistent change in blood pressure variability, as measured in each patient by the standard deviation of the blood pressure values, with SR clonidine. SR clonidine caused a reduction in heart rate that, as that in blood pressure, was well evident throughout the 24 h. It is concluded that SR clonidine is an effective antihypertensive agent and that a single administration of this drug can produce a clear-cut reduction in the blood pressure values of hypertensive patients for a 24-h period.