Resolution of leishmanial infections requires the expansion of specific type 1 T helper cells that secrete or express on their membrane lymphokines capable of activating macrophages that contain these parasites to a microbicidal state. Specific CD8+ T cells, which are triggered during infection, also appear to play a role in protective immunity, possibly through their ability to secrete interferon-gamma. In the mouse model of infection with Leishmania major, the expansion of specific type 2 T helper cells exacerbates disease, an effect that appears to result from the properties of type 2 T helper derived lymphokines to deactivate macrophages and inhibit release of activating cytokines by type 1 T helper cells. In the mouse, destruction of intracellular Leishmania by activated macrophages depends upon the L-arginine-dependent production of nitrogen oxides. Molecules from the parasite that can induce, and are the target of, the protective T-cell response are being characterized.