Highly susceptible BALB/c mice became partially resistant to Leishmania mexicana amazonensis infection after intravenous immunization with solubilized homologous promastigote antigen. Immunized BALB/c mice exhibited mixed mononuclear cell reactions, with granulomatous inflammation, collagen deposition, and fibrinoid necrosis at the site of infection. In contrast, naive animals displayed a monomorphic picture composed of largely vacuolated and parasitized macrophages with areas of coagulative necrosis. Electron microscopy revealed an increased number of eosinophils, sometimes in close contact with parasitized macrophages, in immunized animals. These findings illustrate that histologic changes reflect host immune status in cutaneous leishmaniasis, and that susceptibility of BALB/c mice to L m amazonensis, although dependent on genetic background, can be artificially modified.