Common disorders of water homeostasis leading to polyuria include a variety of endocrine, metabolic, and renal disturbances. After exclusion of most of these conditions, the diagnostic dilemma of differentiating between central diabetes insipidus, primary polydipsia, and nephrogenic diabetes insipidus may remain. Here, we report on 18 young dogs with polyuria that had been present in most cases since the dogs were puppies. The conditions were categorized according to the plasma vasopressin (VP) response to hypertonicity. The VP response to osmotic stimulation was tested by IV infusion of 20% NaCl for 2 hours. The VP response in all dogs was abnormal. Three categories could be distinguished: an exaggerated response (n = 3), a subnormal response (n = 4), and a nonlinear response with high plasma VP concentrations unrelated to increases in plasma osmolality (n = 11). The VP response to hypertonicity did not consistently distinguish among different clinical entities. In the 9 dogs with variations in urine osmolality compatible with primary polydipsia, exaggerated, subnormal, and nonlinear responses were observed. Examination of the present data questions the generally accepted notion that VP measurements during hypertonic saline infusion are the "gold standard" for the diagnostic interpretation of causes of polydipsia and polyuria. Studies of the peripheral reflection in plasma of the pulsatile VP release in healthy and polyuric individuals, with and without osmotic provocation, should be performed.