Mycophenolate mofetil (MMF) is a novel immunomodulator that may be effective in the treatment of chronic active and perianal Crohn's disease (CD). The aim of this study is to assess the efficacy of MMF in CD patients who failed or were intolerant of 6-mercaptopurine (6-MP) or azathioprine (AZA). Eleven CD patients were treated with MMF after a failed course of 6-MP/AZA, and their records reviewed retrospectively. Reasons for 6-MP/AZA intolerance or failure were recorded. Response to MMF was determined by calculation of the Harvey-Bradshaw index and ability to taper steroids. Adverse reactions to MMF were recorded. Eleven patients were identified who failed a previous trial of 6-MP/AZA and other immunomodulators and required immunomodulator therapy. Of 11 patients who started MMF, four had early adverse reactions within 8 weeks and stopped the medication. Of the remaining seven patients who took MMF for at least 8 weeks, one had a complete response, two had a partial response, and four had no response to the medication. In patients who failed 6-MP/AZA, MMF was of benefit in 3 of 11 patients with only one complete responder. This lower-than-expected response rate may indicate that patients who are resistant to 6-MP or AZA may also be resistant to MMF.