A 42-year-old woman was admitted to our hospital because of polydipsia and polyuria. On admission, the daily urine volume was about 6 to 8 L/day, and the plasma arginine vasopressin (AVP) level was undetectable. To determine an involvement of atrial natriuretic peptide (ANP) in maintaining plasma volume homeostasis in the patient with diabetes insipidus (DI), changes of plasma ANP levels were measured during the daytime and after 2.5% hypertonic saline followed by intravenous administration of Pitressin. The plasma ANP level was maintained within a normal range during the day. An intravenous infusion of 2.5% hypertonic saline increased plasma ANP levels, while it failed to increase urine osmolality. The addition of an intravenous bolus of Pitressin (10 U) increased urine osmolality with a decrease of urine volume. Plasma ANP levels showed only a transient decrease at 15 min after Pitressin injection. A daily supplement of 1-desamino-8-D-arginine vasopressin (DDAVP) slightly decreased plasma ANP levels. The present study suggests that an increase in plasma AVP level may not have a direct stimulatory action on ANP secretion in patients with DI.