In this study flow cytometry was used to show that macrophages were the major population of murine peritoneal exudate cells (MPEC), increasing la expression upon treatment with N-acetylglucosaminyl-β1-4-N-acetylmuramyl-alanyl-d-isoglutamine (GMDP). Modulation of la expression resulted from direct action of GMDP on macrophages, rather than from effect of cytokines released by T-cells. The effect of GMDP on two populations of macrophages, namely, slow and rapid responding, was studied in detail. Rapid responding cells were represented by la-positive macrophages: GMDP augmented their la expression. In contrast, slow responding subpopulation was represented by initially la-negative macrophages, in which GMDP induced de novo synthesis of Ia-antigens. The ability to induce Ia expression was also characteristic for other adjuvant-active N-acetylglucosamine-containing muramyl peptides (GMPs). Macrophages were shown to engulf GMPs by endocytosis. Activation of macrophages by GMDP resulted in an increase in their phagocytic activity. © 1995.