A 49-year-old Japanese man with rheumatoid arthritis acutely developed a skin eruption and severe non-productive cough seventeen days after the administration of leflunomide. Because all bacteriology findings were negative, steroid pulse-therapy was initiated promptly due to the rapidity of chest X-ray progression and the deterioration of arterial blood oxygen pressure. Although cough was induced by methotrexate, interstitial pneumonia was not detected clinically before leflunomide administration. He finally died of respiratory failure 128 days after the onset of acute interstitial pneumonia. According to the post-market surveillance, as high as approximately 1.1% of the patients on,leflunomide have developed interstitial pneumonia in Japan. It is important to emphasize that acute interstitial pneumonia due to leflunomide is a very severe and potentially fatal side effect.