It has been demonstrated that hyperprolactinemia is sometimes present even in patients with idiopathic diabetes insipidus (DI). In this study, we examined the responses of serum prolactin (PRL) to hypertonic saline infusion and TRH injection in 11 patients with idiopathic DI diagnosed by clinical examinations. Serum sodium in these patients (147.5 +/- 3.2 mEq/L) was significantly higher at baseline than in normal subjects (139.7 +/- 2.4 mEq/L). The plasma arginine vasopressin (AVP) level was significantly lower in DI (0.42 +/- 0.24 pg/ml) at baseline than in normal subjects (2.53 +/- 1.03 pg/ml). However, the serum PRL level in both groups did not differ significantly except in one patient with idiopathic DI (35.6 ng/ml). There was no significant correlation between the basal serum sodium and basal serum PRL in either group. After an infusion of hypertonic saline, the serum sodium level gradually increased to 155.6 +/- 3.4 mEq/L in DI and to 146.5 +/- 4.3 mEq/L in the normal subjects. However, this increase did not affect PRL secretion in either group. PRL response to TRH was essentially normal in all patients with idiopathic DI. These results indicate that the secretion of PRL is not generally affected by chronic mild hypernatremic hypovolemia in the patients with idiopathic DI.