Organisms of the Mycobacterium avium complex survive the hostile environment of their host cells, the macrophages, and evade immune response, in part, by interfering with processing and presentation of antigen. We studied the effect of infection with M. avium on the expression of the costimulatory/adhesion molecules (referred to herein as accessory molecules) because generating an efficient T cell response requires both the recognition of processed antigen and the participation of accessory molecules. Human peripheral blood monocytes displayed reduced levels of CD54, CD58, and CD86 molecules 1 day after in vitro infection. The reduction in the expression of accessory molecules was not mediated by endogenous IL-10 or prostaglandin because monocytes infected in the presence of either anti-IL-10 neutralizing antibody or indomethacin did not express normal levels of surface CD54, CD58, and CD86 molecules. Consistent with these phenotypic changes, M. avium-infected monocytes were less effective in supporting Ag-independent proliferation of autologous CD4+ T cells.