The response of plasma aldosterone (PA) to ACTH administration (250 micrograms alpha 1-24 ACTH i.m.) before and during treatment with spironolactone (Sp, 75--100 mg/day) for at least 8 months was studied in 11 patients with essential hypertension. These responses were compared with those before and during prolonged treatment with hydrochlorothiazide (Th, 50--75 mg/day), with or without potassium supplement, in 14 hypertensives. PA and plasma cortisol (PC) were determined by radioimmunoassay in which Sp showed minimal cross-reactivity. Both Sp and Th treatments caused similar increases in plasma renin activity accompanied by nearly identical decreases in blood pressure and body weight. PA was also increased by both treatments, but to a significantly greater extent in the Sp-treated group. Serum potassium concentration was increased only by Sp treatment. The response of PA, but not of PC, to acute ACTH stimulation was blunted in the Sp-treated group. That is, the maximal increment of PA above the baseline level was significantly lower during Sp treatment than either before Sp treatment of during Th treatment. These results demonstrate that long-term treatment with Sp can inhibit aldosterone production by acute ACTH stimulation in patients with essential hypertension.