OBJECTIVE To determine whether water handling in patients receiving haloperidol decanoate (HD) was impaired. METHODS Prospective, controlled trial of water handling in patients without symptomatic hyponatremia receiving HD. Eligibility for study inclusion required that patients had received HD for at least 4 months, were not taking any medication reported to cause inappropriate antidiuretic hormone secretion or hyponatremia (excluding haloperidol), and would agree to participate in the study. An age- and gender-matched healthy control subject was enrolled for each study patient. Baseline laboratory values were obtained within 48 hours prior to the standard water-loading test to screen for abnormalities in electrolytes, kidney function, and liver function. A 20-mL/kg water-load test was administered to each patient. Urine volume and osmolality were measured every hour for 4 hours. METHODS A community mental health (CMH) outpatient psychiatric facility for the patients receiving HD and Saint Mary's Health Services for the controls. METHODS Fifteen patients receiving HD from the CMH facility and 15 age- and gender-matched control subjects were enrolled. METHODS Impaired water handling was defined as a failure to dilute urine to less than 100 mmol/kg or a failure to excrete more than 65% of a water load in 4 hours. RESULTS Five patients receiving HD were excluded because of protocol refusal or violation. Five of 10 evaluable patients receiving HD had abnormal water handling. Two of these could not lower their urine osmolality to less than 100 mmol/kg, 2 could not excrete more than 65% of the water load, and 1 did not meet either criteria. None of the healthy volunteers had abnormal free water handling. The difference between the study patients and the control subjects was statistically significant (p = 0.0097). CONCLUSIONS Fifty percent of our study patients receiving HD had abnormal free water handling. This finding, combined with our clinical observations of symptomatic hyponatremia in other patients receiving the drug, suggests the need to investigate the incidence of hyponatremia and to design a useful screening tool to identify patients at risk. In the meantime, clinicians should be aware of the potential for impaired water handling in patients receiving HD.