We examined the local and systemic production of nitric oxide (NO) and the pattern of cytokine during the course of Leishmania mexicana infection in susceptible BALB ⁄ c and resistant C57BL ⁄ 6 mice. NO derivatives were measured in serum, and the expression of inducible nitric oxide synthase (iNOS), interferon (IFN-c), interleukin (IL-4) and epidermal Langerhans cells (LC) was measured in the lesions by immunohistology. Circulating NO concentrations, iNOS+ cell density, IFN-c+ Th1 cells and CD205+ Langerhans cells were higher in early lesions of resistant C57BL ⁄ 6 mice. In contrast, susceptible BALB ⁄ c mice developed chronic and progressive lesions with a predominance of IL-4+ Th2 cells. In both susceptible and resistant mice, lesion size and lymph node volume followed a similar course. The early local and systemic production of NO in resistant mice may be related with the premature production of IFN-c observed, contributing to the resolution of the lesion.