This paper describes a rare case in which the oral administration of mesalamine resulted in the exacerbation of ulcerative colitis (UC) in a patient who was previously responsive to mesalamine and whose colitis had been in remission for eight years. Mesalamine and other 5-aminosalicylic acid compounds are the mainstay of treatment for UC; however up to 8% of patients are unable to take the medications due to intolerance or hypersensitivity reactions. Common drug reactions are fever, nausea, diarrhea and abdominal pain; however, exacerbation of UC has rarely been reported. This study highlights the importance of ruling out mesalamine as the causative agent in cases of UC exacerbations.