The role of infiltrating macrophages in the pathogenesis of acute rejection was investigated in biopsy specimens obtained from human transplanted kidneys using immunohistochemical methods. Thirty-one allograft tissue specimens obtained from 26 patients were histologically classified into 18 with acute rejection, 7 with borderline change and 6 with chronic rejection according to the Banff working classification (1993). These specimens were analyzed by avidin-biotin peroxidase complex method on frozen sections in order to examine the utility of some antimonocyte/macrophage monoclonal antibodies in differentiating acute rejection from other conditions. The ratio of CD68, CD11b, LeuM3, OKM5 and HAM56-positive infiltrating monocytes/macrophages to leukocyte common antigen (LCA)-positive cells in the renal cortex were calculated. As a result, the ratio of the positive cells for CD68, which stains mature macrophages, significantly increased in the cases of acute rejection compared with those of other groups. In addition, a strong expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed in the acute rejection group. In our study, the expression of class II major histocompatibility antigens (HLA-DR) in the proximal epithelial tubules was also strongly observed in the cases of acute rejection. It was thus concluded that the increase of CD68-positive infiltrating cells and the expression of GM-CSF may play a possible role as a reaction effector in the process of acute renal allograft rejection.