A 70-year-old woman with rheumatoid arthritis received treatment with corticosteroids and methotrexate for 4 years, followed by an additional TNF-alpha antagonist (infliximab) for about 3 years. She presented with a several-week history of persistent cough, and CT images of the lung showed a thin-walled cavitary lesion abutting the pleural surface of the left upper lobe. While we investigated the cause of this lesion, we admitted her because of acute chest pain. Chest radiography demonstrated moderate left-sided pneumothorax with pleural effusion. After further investigation, we suspected that her pneumothorax and pleuritis had been caused by a ruptured cavitary lesion arising from a Mycobacterium avium infection. Despite multi-drug therapy, chest tube drainage and surgical pulmorrhaphy her pleural complications were intractable. This is a rare case of pneumothorax and pleuritis caused by Mycobacterium avium infection induced by a TNF-alpha antagonist. Physicians should be aware of nontuberculous mycobacterial infections in patients treated with TNF-alpha antagonists.