Modulation of myelopoiesis by three synthetic muramyl peptides was investigated in vivo. Two adjuvant-active compounds (N-acetylmuramyl dipeptide [MDP] and MDP-butyl-ester) elicited significant responses in DBA/2 mice characterized by a rise in the level of monocyte-macrophage colony-stimulating activity in serum, a proliferation of multipotential stem cells in the bone marrow, and an expansion of granulocyte-macrophage progenitors in the spleen. In contrast, the adjuvant-inactive stereoisomer MDP(D-D) induced only low levels of circulating colony-stimulating activity. Thus, MDP or MDP-butyl-ester injection could induce a greater number of macrophages and therefore enhance both specific and nonspecific immunity.