The macrophage population within and outside plaques from eight cases of multiple sclerosis (MS) (two clinically acute, four chronic progressive and two chronic non-progressive) has been examined in fresh frozen sections with a panel of monoclonal antibodies of macrophage, monocyte and MHC class II specificity. The majority of cells in active, hypercellular plaques, and at active borders, reacted with macrophage- and class II MHC-specific antibodies, and such cells extended beyond the border between demyelinated and myelinated parenchyma. In inactive plaques such cells that reacted with macrophage-specific antibodies were sparse and reacted only inconstantly with class II MHC-specific antibodies. Macrophage heterogeneity was evident in as much as one macrophage antibody, RFD7, reacted only with perivascular and not parenchymal macrophages in most plaques, but reacted with a variable proportion of parenchymal macrophages in active plaques. It is suggested that the RFD7 antibody may identify a sub-population of acute plaques, and that its use may clarify interpretation of findings related to other inflammatory cell populations by providing greater precision of classification of active plaques.