OBJECTIVE To (1) identify abnormalities in arginine vasopressin (AVP, a water-conserving hormone) secretion and release in nursing home (NH) residents with nighttime urinary incontinence (UI); and (2) perform a pilot test of desmopressin acetate (ddAVP, a synthetic analog of the naturally occurring hormone) replacement in these residents. METHODS Diagnostic evaluation and open-label treatment trial. METHODS Two community nursing homes in a metropolitan area. METHODS Male and female NH residents 65 years of age and older with nighttime UI. METHODS Characterizations of AVP status followed by a 7-day open-label trial of oral ddAVP (either 0.1 mg or 0.2 mg). METHODS Water deprivation test results, AVP levels, voided volumes, number of voids, incontinent episodes, number of nighttime checks found wet (out of 6 total checks per night). RESULTS All participants had measurable AVP levels of 2.0 pg/mL or higher. Six of 10 individuals had an abnormal water deprivation test. Two of 4 participants on 0.2 mg of ddAVP and 2 of 6 participants on 0.1 mg had a 200 mL or more mean reduction in nighttime urine volume. Both ddAVP dosages yielded a mean reduction of 0.7 fewer nighttime wet checks found wet. One participant in each group developed hyponatremia (1 of 6 on 0.1 mg and 1 of 4 on 0.2 mg). Hyponatremia resolved with discontinuation of the drug. CONCLUSIONS Both 0.1 mg and 0.2 mg of ddAVP given to carefully screened NH residents for 7 days produced a modest average reduction in nighttime urine volume and number of nighttime incontinent episodes that is likely of little clinical importance. The role of ddAVP in this population requires further research.