In the present study, a set of two monoclonal antibodies (TRPM1, TRPM2) was used to investigate the macrophage populations in the rat thymus and their different sensitivities to cyclosporine-A (CsA). With double immunohistochemical staining we demonstrated that, in the normal rat thymus, there are 3 populations of macrophages (TRPM1+, TRPM1/2+, TRPM2+), present in different proportions throughout the thymus. In the outer cortex TRPM1+ and TRPM1/2+ were present, but the TRPM1/2+ cells were more numerous. No TRPM2+ cells were observed in this area. The cortex and medulla showed all 3 types of cells with a majority of TRPM1/2+ cells. In the corticomedullary zone (CMZ) TRPM1/2+ and TRPM2+ macrophages were present in about equal proportion while only a few TRPM1+ cells were observed. After CsA treatment (for 21 days) profound changes occurred in the thymus; we observed a complete disappearance of the thymic medulla and a reduction in the total number of macrophages. The TRPM1+ macrophages had been eliminated, a few TRPM1/2+ cells were found while many of the cells were TRPM2+. The presence of the macrophages in different thymic areas suggests that they are a very heterogeneous population. The possible significance of the macrophage heterogeneity and the relationship to CsA sensitivity is discussed.