The profile of cytokines induced by soluble leishmania antigen (SLA) and the Leishmania homologue of the mammalian receptor for activated C kinase (LACK), a candidate vaccine against leishmaniasis, and the cellular source of the cytokines produced in response to these antigens were analyzed in patients infected with Leishmania guyanensis. Gamma interferon (IFN-gamma) and interleukin-10 (IL-10) were produced in response to LACK. Although LACK-specific CD4(+) cells producing IFN-gamma were isolated only during the early phase of infection (less than 30 days following the onset of infection), cells producing IL-10 in response to LACK were detected in all patients. CD4(+) T cells producing IFN-gamma and IL-13 were produced in response to SLA in all patients. SLA- and LACK-specific T cells are effector memory cells, as they are CD45RA(-) CCR7(-) CD4(+) T cells. CD4(+) T cells producing IFN-gamma are CD62L(-), and CD4(+) T cells producing IL-10 are CD62L(+), indicating that these cells have different tissue-homing capacities. These findings show that SLA and LACK induce both type 1 (IFN-gamma) and type 2 (IL-10 or IL-13) cell responses.