A relatively simple, standardized 6 1/2 hour water deprivation test is described which adequately differentiates disorders of the neurohypophyseal-hypothalamic system from primary polydipsia. Normal subjects are characterized by an initial serum osmolality between 273 and 293 milliosmoles (mOsm) per kilogram by remarkable constancy of the serum osmolality throughout the 6 1/2 hours and by a urine-to-serum osmolality ratio of 1.9 or greater. Individuals with diabetes insipidus show loss of this homeostatic mechanism to a variable degree. All patients with diabetes insipidus demonstrate defective urinary concentrating capacity. Those patients with diabetes insipidus severe enough to require vasopressin therapy invariably show serum osmolar concentrations of 300 mOsm/kg or greater by the end of the test. Individuals with primary polydipsia demonstrate stability of serum osmolality at normal or slightly below normal levels, while urinary osmolality at the end of the test period is within normal limits.