The development of a Leishmania major protective Th1 response is dependent on IL-12 production. Susceptible BALB/c mice develop a Th2 response. We have previously demonstrated that coinfection with Listeria monocytogenes resulting in type 1 cytokine production (IL-12 and IFN-g), potentiated the response of BALB/c mice to L. major. We investigated here whether Listeriolysin O (LLO), essential for the development of a protective anti-listerial response, was also required to immunopotentiate the response against L. major. Coinfection with L. major and an LLO-producing (LLO+), but not an LLO-nonproducing (LLO–) L. monocytogenes strain, reduced lesion size and parasite load, and increased IFN-g production. Semi-purified LLO also potentiated the response as shown by the containment of parasites in the spleens in well-defined focal granulomas in contrast to controls where more mature disorganized diffuse granulomas with higher parasite loads and necrosis were commonly seen.