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Thiopurines are used as a maintenance therapy in patients with ulcerative colitis (UC). For some patients the metabolism of thiopurines is unfavorable, leading to increased adverse effects, including hepatotoxicity. There are many reports in the adult literature concerning the manipulation of thiopurine metabolism with allopurinol; however, there is only 1 publication in this respect for pediatric UC. We present 3 pediatric cases of UC wherein the combination of allopurinol and low-dose 6-mercaptopurine allowed for shunting of thiopurine metabolites to a more favorable pattern. This intervention supported clinical remission in all, including one case poorly responsive to infliximab.