Two years after being diagnosed with ulcerative colitis, a 57-year-old man taking oral mesalamine experienced severe respiratory distress due to left lung pleuropneumonitis. Eight months later, severe respiratory distress recurred due to right lung pneumonitis. Extraintestinal manifestations of inflammatory bowel disease or mesalamine-induced pulmonary injury were considered in the differential diagnosis, which was complicated by a history of aseptic meningitis and evidence of an ongoing autoimmune response. The implications of the case are discussed.