To search for possible metabolic interactions of α-human-atrial natriuretic peptide (αhANP), we evaluated in 20 normal subjects blood levels of αhANP, glucose, insulin, cortisol, electrolytes, catecholamines, free fatty acids, carnitine and amino acids, blood pressure (BP), and heart rate before, during, and after a 45-min infusion of synthetic αhANP. Group A [n = 10] was studied on liberal and Group B on three consecutive sodium (Na) intakes of 17, 140, and 310 mM/day. Plasma αhANP was slightly but not significantly higher following 5 days on “normal” or high than on low Na+ intakes. ahANP infused at 0.1 μg/kg/min produced on all Na+ intakes comparable percentage increases in plasma insulin (+ 34 to 63%, p < 0.001), norepinephrine (+ 76 to 155%, p < 0.001) and heart rate (p < 0.001), and a similar fall in diastolic BP (p < 0.001). Plasma glucose tended to be decreased slightly and cortisol was reduced; epinephrine, dopamine, and potassium levels were not significantly modified. As evaluated in group A, serum free fatty acids were increased (p < 0.01), plasma free carnitine levels were reduced (p < 0.001), and amino acids were not consistently altered. These findings indicate that in normal humans ahANP may, on various sodium intakes, modulate insulin secretion and/or metabolism and elicit a possibly baroreflex-mediated sympathetic activation and lipolysis.