Controlled heat delivered as radio waves has been used successfully in the treatment of cutaneous leishmaniasis (CL). Here we investigated whether local heat therapy has systemic effects, as measured by the modulation of cytokine production following heat therapy of CL lesions compared with antimonial (Glucantime) treatment. Patients with CL were randomly assigned into this study. Heat (50 degrees C for 30s) was applied once. The control group received Glucantime therapy for 20 d. Cytokine production by peripheral blood mononuclear cells was assayed on days 0, 14 and 28 after onset of treatment. At the end of 28 d, 75% of lesions were healing or healed in the heat therapy group and 90% in the control group (P=0.1261). There was a decrease in IFN-gamma, IL-5 and TNF-alpha levels comparing day 0 with day 28 in both groups, but no difference between the two therapy groups. In patients with only one of several lesions treated with heat therapy, the untreated lesions also healed. Local heat therapy in CL lesions leads to systemic cytokine responses similar to that induced by systemic Glucantime therapy.