Interleukin (IL)-12 contributes to the resistance against a number of intracellular pathogens. We examined the potential biological role of IL-12 by studying peripheral blood mononuclear cells (PBMC), its production and its effect on cytokine synthesis in 20 Sicilian patients with boutonneuse fever (BF) caused by Rickettsia conorii. Data indicate that PBMC from acute BF patients were able to produce IL-12 in response to in vitro stimulation with rickettsial antigen (Ag): this production was higher than that detected in healed patients. Monocytes were the main source of IL-12 by PBMC from BF patients. IL-12 secretion by in vitro Ag-stimulated PBMC from BF patients was potentiated by recombinant interferon gamma (IFN-gamma) or anti-IL-10 monoclonal antibodies (MoAbs). Furthermore, the treatment with anti-IL-12 MoAbs reduced the IFN-gamma synthesis. These results indicate that treatment of PBMC from acute BF patients with IL-12 shifted the response toward a Th1-type cytokine response. Furthermore, IL-12 and IFN-gamma are interdependent and they may be associated with the immunity against rickettsias.