Infection with the Isabel strain of Leishmania has been followed in several inbred strains of mice over an extended period. The mouse strains segregate into three major types with respect to susceptibility to infection: BALB/c, BALB.B and SWR/J are susceptible; DBA/1J is intermediate; and C57BL/6, C57BL/10, DBA/2J and B10.D2 are resistant. Infections with other leishmanial strains have been well-characterized in the BALB/c mice. Therefore, BALB/c mice were selected for extended studies. Progression of the disease was assessed by the following parameters: (1) numbers of parasites isolated from various tissues including footpad lesions, spleens, and lymph nodes and (2) the presence of metastatic lesions. This model should prove valuable in the study of the early immunological events in leishmaniasis.