The ability of interferons (IFN alpha and IFN gamma) to protect human tumour cells from non-MHC-restricted cytotoxicity is well established. We show that in addition to rhIFN gamma, rhTNF alpha is also able to decrease the susceptibility of the human colon carcinoma cell line SW742 to non-MHC-restricted lysis by fresh and IFN alpha activated peripheral blood mononuclear cells. The observed decrease in lysis was not the result of a decrease in the rate of killing. rhTNF alpha and rhIFN gamma were unable to alter MHC class 1 expression, indicating that the protection induced was not the result of increased class 1 antigen expression; however, both cytokines enhanced ICAM-1 expression on the tumour cells. rhTNF alpha and rhIFN gamma did not alter the proliferation or cell-cycle profile of SW742 cells, indicating that the protection was not cell-cycle phase dependent and was not secondary to suppression of cell growth.