The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD.