Leishmania major, the causative agent of cutaneous leishmaniasis in humans, causes either a local cutaneous lesion or a fatal, disseminated infection in different strains of mice. It has been well established that the BALB/c strain of mice is extremely susceptible to L. major infection, due to the preferential development of Th2 responses. It has also been shown, however, that these mice have the potential to develop protective Th1 responses under appropriate conditions. In this paper we confirm earlier reports that BALB/c mice are capable of developing immunity when challenged with low doses of L. major and show that this is dependent on the induction of a Th1 response which can be manipulated with anti-cytokine antibodies in the same way as more conventional experimental infections. Moreover, our data indicate that the development of immunity or susceptibility to L. major in the BALB/c mouse may reflect factors specific to infection such as persistance of the pathogen, infection of APC, or relative cytokine levels rather than simple antigen load, a finding which may be of general significance in infectious disease.