Tumor necrosis factor-alpha (TNFα ) is a cytokine produced by activated macrophages and other cells. In order to verify whether the serum levels of TNFα in American tegumentary leishmaniasis patients are associated with the process of cure or aggravation of the disease, 41 patients were studied: 26 cases of cutaneous leishmaniasis (CL) and 15 of mucocutaneous leishmaniasis (MCL). During active disease the serum levels of TNFα of MCL patients were significantly higher than those of CL patients and control subjects (healthy individuals and cutaneous lesions from other etiologies). The MCL patients had serum titers of TNFα significantly lower at the end of antimonial therapy than before therapy. After a six-month follow-up, the MCL patients had serum levels of TNFα similar to those observed at the end of the therapy as well as to those of CL patients and control subjects. No significant variation in the serum levels of TNFα was observed in CL patients throughout the study period (before, at the end of therapy and after a six-month follow-up). The possible relationship between the high TNFα serum levels and severity of the disease is discussed.