We examined the neuropsychological sequelae of water intoxication in nine schizophrenic patients with the syndrome of psychosis, intermittent hyponatremia and polydipsia (PIP). Patients were assessed using a standardized test battery on two occasions following laboratory blood work: once during hyponatremia (serum sodium < 130 mmol/l) and once during normonatremia (serum sodium > 136 mmol/l). Results revealed significant deficits during hyponatremia involving complex information processing skills such as mental flexibility and verbal fluency. In contrast, short-term memory was intact and no deficits in sustained attention or visual-motor scanning were observed. Our results underscore the dramatic fluctuations in neuropsychological functioning due to metabolic and osmotic changes during water loading in PIP syndrome patients. In addition, we found that the neuropsychological effects of hyponatremia are remarkably consistent across patients. These complications, if not recognized, are likely to contribute to worsening of psychosis despite appropriate pharmacological treatment while severely limiting patient ability to actively participate in behavioral interventions.