In the pathogenesis of most experimental autoimmune diseases T lymphocytes play a crucial role in the initiation, whereas macrophages are essential in the effector phase. This review deals with several methods to elucidate the exact role macrophages play in different stages of autoimmune models in the rat. By using monoclonal antibodies an inventory has been made on the different macrophage subsets that are present in the infiltrates of the affected tissues. That macrophages play a decisive role in provoking the clinical signs has been shown by several macrophage elimination studies. The severe tissue damage caused by macrophages is brought about by the release of inflammatory mediators. Especially interference with the production or action of these products could provide new therapeutical means.