B-1 cells are a subtype of B cells with peculiar characteristics. These cells are distinct from B-2 lymphocytes in their morphology, ontogeny, tissue distribution, and phenotypic functional features. B-1 cells can participate in the immune response in several ways, for example, by being recruited to inflammatory foci, producing large amounts of IL-10 cytokine, and differentiating into IgM-secreting cells or phagocytes. Nevertheless, the role of B-1 cells in the pathogenesis of experimental leishmaniasis has not been fully elucidated. Here we evaluated the role of B-1 cells in Leishmania (L.) amazonensis infection using X-linked immunodeficient (XID) mice that possess a mutation in Bruton's tyrosine kinase (Btk) that leads to a reduced number of B-1 cells. The course of infection and the corresponding immune response were analyzed in infected mice. XID mice showed an increase in parasite number in paws, lymph nodes, and spleen compared to BALB/c infected controls. Infected XID mice had higher IL-10 levels and lower anti-Leishmania IgM. The adoptive transfer of peritoneal B-1 cells into XID mice restored peritoneal B-1 cells and parasite burden in the footpad in a pattern similar to that observed in the BALB/c controls at 10 wk. Our results demonstrate the higher susceptibility of XID mice to infection with L. (L.) amazonensis compared to controls. In addition, we show that the presence of B-1 cells contributes to improved animal resistance to parasites, suggesting that these cells are involved in the control of cutaneous infection caused by L. (L.) amazonensis.