The immunoreactivity of lymphocytes from mice bearing large tumors was investigated. As compared to normal lymphocytes, lymphocytes from tumor bearers manifested a lessened proliferative response to T-cell mitogens and were less capable of destroying syngeneic tumor target cells. However, the impaired reactivity of these lymphocytes was improved significantly after washing repeatedly in tissue culture medium in vitro. The increase in cytolytic activity was tumor specific. A membrane-associated

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... uppressive substance was detected in the washing medium which inhibited the cytotoxicity of washed lymphocytes. The effect of suppressive substance was tumor specific and sensitive to treatment with protein A and anti-immunoglobulin antibody, indicating that the suppressive substance contained immunoglobulin. The present findings suggest that a membrane-associated suppressive substance(s) may be in part responsible for the diminished immune responsiveness of lymphocytes from animals bearing large tumors.