The antihypertensive, renal hemodynamic, and humoral effects of pinacidil and hydralazine monotherapy were compared in a double-blind study. Supine diastolic blood pressure decreased with pinacidil (n = 14) from 96.5 to 82.6 mmHg (p less than 0.05), after a mean of 8.5 weeks at a mean dose of 64.3 mg/day, and with hydralazine (n = 15) from 101.5 to 94.0 mmHg (p less than 0.05), after 8.3 weeks at a dose of 163.3 mg/day. Renal plasma flow, glomerular filtration rate, and urinary albumin excretion did not change with pinacidil or hydralazine therapy. Neither agent altered plasma renin activity. Supine and upright plasma aldosterone concentrations decreased significantly during pinacidil, but not during hydralazine, therapy. Thus, both pinacidil and hydralazine reduced blood pressure and preserved renal function. During pinacidil therapy, plasma aldosterone concentrations decreased, whereas plasma renin activity did not. The mechanism of this response is unclear.