SummaryThe growth ofLeishmania majorandLeishmania mexicanalesions and the concomitant development of delayed‐type hypersensitivity (DTH) to homologous or heterologous soluble antigen was studied in BALB/c and CBA/Ca mice. Although CBA/Ca mice are highly susceptible toL. mexicana, developing non‐healing lesions, they are resistant toL. major; while BALB/c mice develop non‐healing lesions when infected with either species. The development of resistance was associated with the acquisition of DTH which peaked at 48 h (L. majorinfected CBA/Ca mice). Non healing lesions were associated with either negative DTH (L. majorinfected BALB/c mice) or DTH that peaked at 24 h but had significantly subsided by 48 h (L. mexicanainfected CBA Ca and BALB/c mice). The latter response was associated with basophilic infiltration of the skin test site. Pre‐irradiating (600 rad) CBA/Ca and BALB/c mice induced resistance againstL. mexicanaandL. majorrespectively in conjunction with the appearance of 48 h DTH to the homologous antigen. There was clear dissociation in the skin reactivity produced by the heterologous antigen. ThusL. major‐derived antigen failed to produce DTH inL. mexicanainfected mice of either strain.L. mexicana‐derived antigen on the other hand produced a quicker response and of greater magnitude than the homologous antigen inL. majorinfected CBA/Ca mice. This correlated well with the strong cross‐immunity induced byL. majorin these mice toL. mexi