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Neuroleptic malignant syndrome (NMS) is a rare, life-threatening idiosyncratic reaction secondary to antipsychotic medications. NMS is characterized by muscular rigidity, fever, autonomic instability, and an altered level of consciousness and it is usually accompanied by rhabdomyolysis. This syndrome is supposed to result from an excessively rapid blockade of postsynaptic dopamine receptors. It is well known that severe hyponatremia can cause neurologic complications such as stupor, seizures, and even coma. Hyponatremia frequently develops in elderly patients and also psychiatric patients. We have reported an elder patient with recurrent depression taking venlefaxine and olanzapine therapy, who developed overt NMS following hyponatremia. A 64-years-old male was admitted to the Emergency Department of a State Hospital due to symptoms including changes in mental status, nausea-vomiting, fever and loss in eating function. Patient’s hyponatremia (serum Na: 121 mEq/l) was confirmed and treated in the hospital. However, the symptoms started again immediately after discharge and was gradually intensified. Progressively, he had lethargy. He was admitted to our hospital because of unconsciousness, fever, marked muscle rigidity and motor immobility. His psychiatric history revealed that he was diagnosed to have recurrent depression 6 years ago. He was regularly given oral venlefaxine 150 mg daily and oral olanzapine 2,5 mg daily. He received 10 mg daily olanzapine due to insomnia 5 days before admission. At admission, his body temperature was 36.7 °C and the blood pressure was 160/95 mm Hg. He was extremely rigid and unresponsive. On admission, laboratory tests revealed: total leukocytes count 10.77 K/uL, Serum muscle enzymes were markedly elevated: CPK 431 u/L (normal up to 200). Antipsychotic drugs were withdrawn after admission; bromocriptine 7.5 mg daily was initiated. Ten days later, the patients’ muscle rigidity and other symptoms resolved, and serum CPK level was normalized (37 u/L). The treatment of bromocriptine was gradually stopped. The patient was discharged on the 19th day after admission. We presented a case of neuroleptic malignant syndrome secondary to hyponatremia. The development of hyponatremia has been facilitated because of the patient’s being an elderly person. Hyponatremia associated with neuroleptic malignant syndrome has been described as a syndrome of inappropriate secretion of antidiuretic hormone. It was known that patients with psychiatric disorders such as psychosis and depression have a propensity to develop hyponatremia. Psychogenic drugs such as haloperidol, şuphenazine and thioradazine cause hyponatremia by unknown mechanisms. This patient has used venlefaxine and low dose olanzapine for the last 6 years. NMS developed after increasing the dose of olanzapine. In conclusion, this report shows that NMS may occur following hyponatremia; therefore this combination needed to be used with caution in patients with depression. Metabolic changes in elderly patients with depression may lead to life-threatening problems. Clinicians should inform their patients sufficiently about the use of drugs and drug dose.