To determine factors associated with the development of encephalopathy and with its clinical course in patients with postoperative hyponatremia. Consultation and referral services of two university medical centers and community hospitals. Case-control study (risk factors for encephalopathy) and cohort study (clinical course among patients with encephalopathy). Case patients included 65 adults with postoperative hyponatremic encephalopathy; controls included 674 adult patients who had postoperative hyponatremia without encephalopathy and who were selected from 76,678 consecutive adult surgical inpatients. Age, gender, menstrual status, neurologic symptoms, time to development and degree of hyponatremia, arterial blood gas determinations, serum chemistries, morbidity and mortality. Case patients included 40 women (62%) and 25 men (38%) (P > 0.05); controls included 367 women (54%) and 307 men (46%) (P > 0.1). Of the 34 case patients who developed permanent brain damage or died, 33 (97%) were women (P 0.1). Women and men are equally likely to develop hyponatremia and hyponatremic encephalopathy after surgery. However, when hyponatremic encephalopathy develops, menstruant women are about 25 times more likely to die or have permanent brain damage compared with either men or postmenopausal women.