To search for possible metabolic interactions of alpha-human-atrial natriuretic peptide (alpha hANP), we evaluated in 20 normal subjects blood levels of alpha hANP, 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 alpha hANP. 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 alpha hANP was slightly but not significantly higher following 5 days on "normal" or high than on low Na+ intakes. alpha hANP infused at 0.1 microgram/kg/min produced on all Na+ intakes comparable percentage increases in plasma insulin (+34 to 63%, p less than 0.001), norepinephrine (+76 to 155%, p less than 0.001) and heart rate (p less than 0.001), and a similar fall in diastolic BP (p less than 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 less than 0.01), plasma free carnitine levels were reduced (p less than 0.001), and amino acids were not consistently altered. These findings indicate that in normal humans alpha hANP may, on various sodium intakes, modulate insulin secretion and/or metabolism and elicit a possibly baroreflex-mediated sympathetic activation and lipolysis.