In this review the role of various subpopulations of macrophages in the pathogenesis of experimental autoimmune encephalomyetitis is discussed. Immunohistochemistry with macrophage markers shows that in this disease different populations of macrophages (i.e. perivascular cells, microglia and infiltrating blood-borne macrophages) are present in the central nervous system. These subpopulations partially overlap in some functional activity while other activities seem to be restricted to a distinct subpopulation, indicating that these subpopulations have different roles in the pathogenesis of encephalomyelitis. The studies discussed in this review reveal that immunocytochemical and morphological studies, combined with new techniques such as in situ nick translation and experimental approaches like the use of bone marrow chimeras and macrophage depletion techniques, give valuable information about the types and functions of cells involved in central nervous system inflammation. The review is divided in three parts. In the first part the experimental autoimmune encephalomyelitis model is introduced. The second part gives an overview of the origin, morphology and functions of the various subpopulations. In the third part the role of these subpopulations is discussed in relation to the various stages (i.e. preclinical, clinical and recovery) of the experimental disease.