Treatment of persistent leishmaniasis with oral agents has received increasing attention, although the optimal agent for use in all settings has not been determined. This report describes a patient with persistent cutaneous infection due to Leishmania mexicana mexicana who apparently responded to therapy with allopurinol after treatment with a course of ketoconazole failed. In vitro testing of pre- and posttreatment isolates from the wound did not demonstrate the development of resistance to ketoconazole. To our knowledge, this is the first report that independently confirms the recently reported efficacy of allopurinol for treatment of leishmaniasis.