The Major Outer Membrane Protein (MOMP) belongs to the membrane complex of cysteine-rich proteins of Chlamydophila pneumoniae. Although MOMP can elicit strong immune responses it fails to confer long-term protection against infection in animal models. This effect has been attributed, at least in part, to an inadequate induction of protective Th1-mediated immune responses. In an effort to understand the cellular mechanisms associated to the immunomodulatory properties of MOMP we studied the effect of this protein on mouse macrophages and naïve T-lymphocytes. We found that incubation of mouse macrophages with recombinant MOMP (rMOMP) results in an increased secretion of MMP-9 and a down-regulation of MHC class II, CD86 and CD40. This was accompanied by an increase in IL-10 and IFNgamma but not in IL-12 secretion. rMOMP induced a down-regulation of the expression of CD69 and CD154 markers by activated CD4(+) T cells, and enhanced the secretion of IL-2 and IL-10 by these cells. Conversely, rMOMP-treated macrophages up-regulated the expression of CD69 but not CD154, inhibited the synthesis of IL-10 and up-regulated the production of IFNgamma by activated CD8(+) T cells. Immunization of mice with MOMP induced the synthesis only of MOMP-specific IgG1 but no differences in cytokine profile were observed compared to controls. Our results provide new evidence on the role of MOMP in modulating T cell-mediated immune responses.