Forty-three patients with mild essential hypertension were randomized into two double-blind studies: pinacidil vs. placebo or pinacidil vs. hydralazine. Pinacidil (62±18 mg/day) decreased office systolic and diastolic blood pressures from 145 to 137 mm Hg and from 98 to 89 mm Hg, respectively, after 6 weeks of therapy. Similarly, hydralazine (128±28 mg/day) reduced supine systolic blood pressure from 140 to 134 mm Hg and supine diastolic blood pressure from 93 mm Hg to 84 mm Hg. Significant tachycardia was not noted with either drug. Ambulatory blood pressure was monitored for 24 h during the placebo-washout and efficacy phases with both pinacidil and hydralazine. Mean 24-h blood pressure was 128 systolic and 81 diastolic with pinacidil and 121 systolic and 76 diastolic with hydralazine. Reduction in awake hypertensive diastolic blood pressure was significant for both pinacidil and hydralazine. Normal sleep diastolic blood pressure was not reduced by pinacidil but was reduced by hydralazine. Side-effects with both drugs included edema, headache, and palpitations. These data demonstrate that pinacidil is as effective an antihypertensive agent as hydralazine.