We here report a case presenting with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after having been treated for pleurodesis with OK-432, which is a lyophilized preparation of an attenuated strain of Streptococcus pyogenes. The patient, who had undergone a subtotal esophagectomy 4 years previously, was referred to our department after the diagnosis of a metastatic lung tumor. A right lower lobectomy of the lung was performed, and prolonged air leakage from a pulmonary fistula thereafter developed because of the dissection of severe pleural adhesion. OK-432 (5 klinische einheiten) was administered to the pleural cavity 3 times. On the 13th postoperative day, the patient began to complain of general fatigue and nausea. SIADH was diagnosed based on laboratory findings such as hyponatremia, serum hypo-osmolality and a high excretion of sodium in the urine. A restriction of the fluid intake with a sodium supplement resulted in the return to a normal serum level within 2 weeks. We therefore concluded that the intrapleural instillation of OK-432 had apparently caused SIADH in this case, because no other causes could be found.