The mononuclear phagocytic system is composed of cells which display a marked immunohistological heterogeneity. In the present study we have investigated the immunohistochemical and enzymatic features of macrophages and accessory cells present in human lymph nodes and spleen and, as control tissues, in thymus, liver, skin and heart. Our investigation has demonstrated that macrophages present in germinal centres display an immunophenotype different from that of macrophages populating T-dependent areas. Furthermore, cells lining lymph node sinuses and splenic sinusoids express endothelial and macrophage markers, and are able to modulate their immunophenotype according to different reactive conditions. These data suggest, on immunohistochemical grounds, that macrophages populating B- and T-dependent areas as well as sinuses of human peripheral lymphoid tissues, may modulate their immunophenotype according to environmental and antigenic influences.