We describe a patient with acquired T-helper lymphocyte anergy to mycobacteria following infection with Mycobacterium ulcerans. Before infection, the patient's peripheral blood mononuclear cells responded to in vitro stimulation with M. ulcerans by producing Th1 cytokines, but, after she developed an ulcer, the response was shifted toward production of Th2 cytokines. Immunomodulatory therapy may be an effective intervention for Buruli ulcer.