Purpose: Azathioprine (AZA) is a widely used immunomodulator in the treatment of inflammatory bowel disease (IBD). AZA has been associated with hepatotoxicity. Such hepatotoxicity can occur as an idiosyncratic reaction in the form of cholestatic jaundice or a hypersensitivity reaction with hepatocellular injury. Alternatively, it can be dose-dependent in the form of transaminitis, nodular regenerative hyperplasia, veno-oclusive disease, peliosis hepatitis, etc. Here, we report a rare case of AZA induced immunoallergic hepatitis: A 50-year-old female with a 5-year history of ileo-colonic Crohn's disease (CD) was started on AZA due to diarrhea and lower abdominal pain that were not controlled on 5-aminosalicylates. The patient's thiopurine methyltransferase activity was normal. Weekly monitoring of hepatic function profile for 5 weeks showed normal results. On week 6, the ALT and AST rose for the first time to 190 and 117 U/L. At week 7, ALT and AST further increased to 290 and 159 U/L, respectively. AZA was stopped with rapid decline of the enzymes back to normal within 10 days. During this period, the patient stated she may have had an upper respiratory infection, but denied any Tylenol, herbal medicine, alcohol or recreational drug intake. Viral serology for hepatitis A, B and C were all negative. Serum ANA, ASMA, ceruloplasmin, iron, transferrin saturation, ferritin were normal. Quantitative PCR for CMV in blood was negative. Peripheral smear did not suggest EBV infection. US and MRI of the abdomen revealed no evidence of biliary obstruction or other liver diseases. Concomitant treatments were lanzoprazole, hydrochlorothiazide, metoprolol, and mesalamine; and none of these had been recently introduced or withdrawn from the patient. After discussing potential treatment options and the risks of rechallenge, AZA was restarted at 25 mg daily. Upon rechallenge with a single dose, the patient began having flu-like symptoms, fatigue, nausea, vomiting and diarrhea within 24 hours. Further treatment with AZA was stopped. Her ALT and AST rose to 374 and 280 U/L in 24 hours; and continued to peak at 823 and 652 U/L, respectively, at 48 hours. Peak AP was 229 U/L and peak total bilirubin was 1.4 mg/dl. Of the six IBD cases reported to have idiosyncratic reactions to AZA to date, most are male, and the two CD cases have had cholestatic injury. This is the first case of CD with clear cut hepatocellular hypersensitivity reaction after a single ½ tablet rechallenge. The rapid rise in enzymes with minimal challenge within hours to levels far above the previous levels of elevation in our case suggests further caution, and requirement for daily LFTs in any patient undergoing a re-challenge protocol.