Central dopaminergic mechanisms involved in the regulation of plasma aldosterone concentration were investigated in 16 conscious sheep following Na depletion with intramuscularly administered furosemide. Intracerebroventricular infusion of dopamine (20 μg/min) decreased plasma aldosterone significantly to 52 ± 8% of basal level and increased plasma renin activity (PRA) significantly to 172 ± 25% of basal level in this animal model. In addition, intracerebroventricular infusion of the dopamine antagonist metoclopramide (20 μg/min) in artificial cerebrospinal fluid vehicle significantly increased aldosterone levels to 144 ± 14% of basal level and decreased PRA to 62 ± 5% of basal value. Neither intracerebroventricular infusion of the vehicle nor intravenous infusions of metoclopramide or dopamine at the same doses changed aldosterone or PRA levels. Intracerebroventricular bolus injections of metoclopramide (20 μg/kg in 0.4 ml of vehicle) were also effective, increasing aldosterone levels to 266 ± 22% of basal level and decreasing PRA to 70 ± 12% of basal level. Intravenous bolus injections of the same dose of metoclopramide were ineffective. Dopamine was infused intracerebroventricularly into two uniadrenalectomized sheep with the remaining adrenal transplanted to the neck. Aldosterone levels were decreased to 49 ± 10% of basal level, and PRA was increased to 157 ± 10% of basal value. None of the infusions or injections changed arterial or intracranial pressure, or plasma K, Na, and cortisol levels. These data indicate that endogenous or exogenous dopamine may act on central dopamine receptors to decrease plasma aldosterone concentration by an unknown humoral mechanism. The known aldosterone regulators, plasma Na, K, angiotensin II, and adrenocorticotropic hormone, are not involved in the regulation.