In our preceding study, we showed that infection of mice with Mycobacterium microti leads to a dramatic increase in Ia expression on local inflammatory macrophage populations. However, the majority of these cells did not contain intracellular organisms. To evaluate the effect of parasitism of macrophages by M. microti, Ia-induction experiments were performed in vitro. We show here that Ia expression is increased on peritoneal macrophages treated with either crude lymphokine preparations or recombinant gamma-interferon (gamma-IFN) and that this expression is suppressed by M. microti in a dose dependent fashion. The degree of suppression varied between macrophage populations and could be achieved to a lesser extent with killed organisms. It was partially reversed with indomethacin but only poorly so at high infection levels. Inhibition of Ia expression may be of importance in the generation and maintenance of chronic infection.