Colonic tissue membrane binding to peripheral blood mononuclear leukocytes was quantitated by 125I labeling of membrane fragments and by determining the acquisition of membrane-specific enzyme activity and radioactivity in mononuclear cells after contact with the tissue membrane fragments. Mononuclear cells bound equal amounts of normal and tumor tissue membrane fragments. Mononuclear cells capable of binding homologous but not autologous colonic tissue membranes were recovered from the peripheral blood of colon cancer-bearing patients. Mononuclear cells capable of binding autologous colonic tissue membranes appeared in the peripheral blood of patients after curative but not palliative tumor resection. Tumor membrane enzymes, including alkaline phosphatase, were introduced to mononuclear cells by bound tissue fragments. The activity of alkaling phosphatase present in the bound membrane fragments was inhibited by the immunorestorative drug, levamisole. Cellular debris liberated from tumors may play an important role in overcoming the host's defenses by binding to mononuclear cells, saturating antigen-binding sites, and introducing exogenous enzymes.