Costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are indispensable for T-cell activation. Recently, a paucity of these costimulatory molecules was reported in inflammatory cells in colon cancer, which may permit the immune evasion of the cancer. The present study uses immunohistochemistry to reveal the expression of these molecules in 43 cases of colorectal cancer tissue. B7-2 was expressed in mononuclear calls distributed along the invasive margin in 37 of 43 cases. B7-1 was positive in the same area in 22 cases. In contrast, the expression of B7-1/B7-2 was usually inconspicuous in the stroma within cancer. Most B7-1+ and B7-2+ cells were identified as macrophages because of the coexpression of CD68 antigen or acid phosphatase activity. CD4+ or CD8+ T cells were distributed in the same area and were in close contact to B7-1/B7-2+ cells. Both CD4+ and CD8+ T cells had a proliferative activity with a labeling index of Ki-67 of 1.5% and 2.5%, respectively. Conventional electron microscopy confirmed both the accumulation of macrophages along the invasive margin and the attachment of lymphocytes to them. Immunoelectron microscopy confirmed: (a) localization of B7-2/B7-1 along the cell membrane; (b) abundance of vacuoles and heterophagosomes (a finding indicative of phagocytosis of other cells) in the cytoplasm of these cells; and (c) direct cell-to-cell contact between these macrophages and lymphocytes. The present data, which suggest that an immune reaction occurs along the invasive margin of colorectal cancer, are in accordance with previous clinicopathologic studies suggesting that peritumoral lymphocytic infiltration is one of the favorable prognostic factors in this disease.