The effect on blood pressure of giving hydralazine orally, 300 mg per day divided into 2, 3, and 4 doses, was studied in 4 hypertensive patients. There was no significant difference in average mean arterial pressure for the 3 regimens. Fluctuations of mean arterial pressure with time were not significantly different for the regimens as indicated by coefficient of variation. The mean coefficient of variation for the 2 days prior to initiation of hydralazine dosing was 4.0% +/- 0.3 (SEM) and for the 3 dosing regimens ranged from 4.1% to 4.8%. Heart rate was used as an index of vasodilator-induced increase in sympathetic tone and therefore as a measure of possible side effects. Fluctuations in heart rate were small and were not associated with symptoms. After discontinuation of hydralazine, the time for blood pressure to return halfway between initial placebo value and end treatment value varied from 30 to 140 hr. A tracer dose of hydralazine 14C. HCl was administered intravenously to the patients. The urinary excretion of 14C showed a multiexponential pattern of elimination with a previously undescribed prolonged terminal phase. Under the conditions of the present study, a daily dose of 300 mg of hydralazine was as effective and free of side effects given in 2 as in 4 divided doses.