Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity (PRA), aldosterone, norepinephrine, and cortisol, and renal functions were investigated in nine children with diabetic ketoacidosis. Before therapy, blood glucose concentration was 608.4 +/- 142.2 mg/dL and base excess -21 +/- 1.9 mmol/L. The calculated volume depletion was 2505 +/- 1005 mL/1.73 m2. At the onset of the study, the plasma concentration of ANP (5.3 +/- 1.2 fmol/L) was low, and concentrations of AVP (159 +/- 44 pg/mL), PRA (59 +/- 19 ng angiotensin l/mL/hr), aldosterone (114 +/- 11 ng/dL), norepinephrine (430 +/- 67 pg/mL), and cortisol (33 +/- 2.1 micrograms/dL) were markedly elevated. Fluid replacement raised plasma ANP concentration, which reached physiologic levels on the first day of therapy. PRA, aldosterone, norepinephrine, and cortisol also normalized during the first 24 hours of therapy, whereas AVP remained above the physiologic range at 20.4 +/- 6.8 pg/mL on the third day. Our data indicate that in diabetic ketoacidosis, volume depletion, enhanced sodium excretion, and hyponatremia activated vasoconstrictor and sodium-retaining hormone systems and that secretion of the natriuretic and vasodilator hormone ANP is suppressed. All of these hormonal alterations seem directed at maintaining adequate fluid volume and sodium homeostasis.