The possible involvement of peripheral dopaminergic mechanisms in the action of atrial natriuretic peptides was investigated in 10 subjects by administering 200 micrograms h-ANP 99-126 intravenously for 30 min during treatment with 50 mg carbidopa, a peripheral inhibitor of dopamine synthesis, every 8 h, or during placebo. Atrial natriuretic peptide (ANP) infusion during placebo was associated with a significant increase of diuresis, natriuresis, kaliuresis, urinary noradrenaline, and dopamine excretion. Plasma aldosterone significantly decreased. Blood pressure was slightly reduced. The administration of carbidopa significantly reduced urinary dopamine excretion but did not modify natriuresis, diuresis, indexes of adrenergic and renin-aldosterone system activity, blood pressure, or heart rate, both in basal conditions and in response to ANP infusion. We conclude that the effects of exogenous ANP administration are independent from dopaminergic mechanisms that involve the synthesis of dopamine outside the central nervous system, particularly in the kidney.