OBJECTIVE To report a case of mercaptopurine-induced fever. METHODS A patient with Crohn's disease was treated with mercaptopurine (6-MP) for an exacerbation of his illness. The patient developed fever and chills. After thorough diagnostic examinations and failure to respond to antimicrobial therapy, symptoms were attributed to an allergic-type reaction to 6-MP. The patient defervesced after 6-MP withdrawal. Fever and chills, along with arthralgias, recurred upon rechallenge with a single dose of 6-MP. CONCLUSIONS Adverse effects attributable to 6-MP therapy in inflammatory bowel disease were reviewed in the literature. Drug-induced fever has been previously reported; however, it is an uncommon adverse effect and is difficult to diagnose. It is also difficult to predict which patients will have the reaction. It is a diagnosis of exclusion requiring a thorough investigation. CONCLUSIONS Drug-induced fever should be considered when confronted with fever and chills in patients with inflammatory bowel disease being treated with 6-MP. This case report shows the difficulty in differentiating between an infectious process and an adverse reaction to a medication.