Non-tuberculous mycobacterium infection is rarely accompanied by pleural involvement. We report a very rare case of Mycobacterium avium-intracellurare complex (MAC) pleuritis with massive pleural effusion. The patient was a non-compromised 67-year-old female and had been treated for pulmonary non-tuberculous mycobacterium infection. She was admitted to hospital because of general malaise, low-grade fever and right pleural effusion. Cytological examination of the effusion did not show malignant cells. MAC was only identified by culture and PCR. No other bacteria were detected. Complete resolution of the pleural effusion occurred after administration of anti-tubercular agents (isoniazid, rifampin, ethambutol) and clarithromycin.