We studied the changes in plasma arginine vasopressin (AVP) and urinary excretion of aquaporin-2 (UAQP-2) water channel in 3 patients with diabetic ketoacidosis. They had marked hyperglycemia of 27.9 ± 2.8 mmol/l (mean ± SEM), and elevated hemoglobin A1c of 8.8 ± 1.4%. Circulatory blood volume was decreased by approximately 25%, which was determined by the changes in hematocrit. Plasma AVP levels were elevated to 10.3 ± 3.0 pmol/l and UAQP-2, 578 ± 200 fmol/mg creatinine (normal, 153 ± 28) at the hospitalization. When hyperglycemia was improved by the intravenous infusion of a small dose of insulin plus fluid administration, both plasma AVP and UAQP-2 promptly decreased to 1.2 ± 0.2 pmol/l and 252 ± 29 fmol/mg creatinine on day 7, respectively. These alterations were concomitant with the recovery of circulatory blood volume. In the present study, UAQP-2, in addition to plasma AVP, indicates circulatory blood volume depletion, and the changes in UAQP-2 estimates the AVP-dependent recovery of circulatory blood volume during the therapeutic period in the patients with diabetic ketoacidosis.