Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a well-characterized hematopoietic growth factor. Recently, using purified recombinant-derived material, we have found that GM-CSF is also a potent activator of mature functional macrophages. Thus, we have found that exogenous GM-CSF augments the primary plaque-forming response to sheep red blood cells and that this effect is due to upregulation of Ia antigen expression and interleukin 1 production by the macrophages. We also show that GM-CSF inhibits the replication of Trypanosoma cruzi in cultured peritoneal macrophages and causes an accelerated clearance of Salmonella typhimurium from the peritoneal cavity of mice. These data indicate that GM-CSF is a multifunctional molecule stimulating both hematopoiesis and mature macrophage function.