American visceral leishmaniasis (AVL) is associated with the absence of lymphocyte proliferative responses and interleukin (IL)-2 and interferon-γ (IFN-γ) production upon stimulation with Leishmania antigen. In contrast, cure of AVL is associated with restoration of these T cell functions. In the present study, the ability of IL-12, a cytokine that acts on NK and T cells to restore cellular immune responses in AVL, was evaluated. Participants of the study included 12 patients with AVL and 7 subjects cured of AVL. The [³H]thymidine uptake and IFN-γ production in cultures of peripheral blood mononuclear cells (from AVL patients) stimulated with Leishmaniachagasi antigen were 882 ± 1393cpm and zero, respectively. Addition of IL-12 enhanced the proliferative response to 5097 ± 6429 cpm (P < .001) and IFN-γ production to 305 ± 325 pg/mL (P < .01). IL-12 also restored cytotoxic activity against the K562 cell line. These results indicate that IL-12 has an important role in the regulation of the cellular immune response in human leishmaniasis.