Using immunohistochemical techniques and a panel of murine monoclonal antibodies that recognize rat cells of the mononuclear/phagocyte lineage, it has been demonstrated that the cells labelled with these antibodies are widely distributed throughout the perimysial and endomysial sites in the rat skeletal muscle. These cells have a distinctive dendritic morphology and form phenotypically heterogenous populations. Double immunoperoxidase staining with the monoclonal antibody and anti-Von Willebrand factor antiserum, which recognize vascular endothelial cells, revealed that most of these resident macrophages are closely associated with microvasculature. The perivascular location of these cells suggests that at least some of the resident macrophages may be pericytes. These observations indicate that the macrophages form an important component of the non-muscle cell population in the muscle tissue, and may be intimately involved in various immunopathological conditions of the skeletal muscle.