Five cases of central diabetes insipidus (CDI) in domestic shorthair cats are described. All cats were under 3 years of age at the onset of clinical signs, and outdoor or outdoor/indoor cats, in which a prior trauma was either present or possible. The history included polydipsia and polyuria, and physical examination abnormalities included urinary bladder distention and dehydration. All cats had hyposthenuria with a urine specific gravity between 1.003 and 1.006. The diagnosis was confirmed by an observed inability to concentrate urine during a water deprivation test or compatible serum osmolality, followed by an increase in urine concentration after desmopressin administration. All cats in this report were treated successfully with oral desmopressin. The dose (25–50 μg q8–12h) and the response to therapy were variable. Oral desmopressin administration may serve as an effective alternative route for cat owners who find the conjunctival or nasal application of the solution an inconvenient mode of therapy.