Nephrogenic diabetes insipidus was diagnosed in two full sibling Thoroughbred colts. Each colt had a history of excessive urination. Extreme polydipsia (greater than 80 L per day) was documented in both colts. Inability to concentrate urine in response to water deprivation, infusion of hypertonic saline, or exogenous vasopressin administration indicated insensitivity of the collecting duct epithelial cells to vasopressin. A diagnosis of nephrogenic diabetes insipidus was further supported by a normal increase in plasma vasopressin concentration after water deprivation in the one colt in which such testing was pursued.