Intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha receptor (TNF-R) have been detected in soluble forms in the serum of cancer patients. sICAM-1 can abrogate non MHC-restricted cytotoxicity mediated by NK and lymphokine-activated killer cells. Soluble TNF-alpha receptors have been shown to neutralize the cytopathic activity of recombinant TNF-alpha. Both mechanisms can facilitate neoplastic cells to escape immunosurveillance. Serum levels of sTNF-R and sICAM-1 were determined during a phase II combination trial with TNF-alpha and IFN-gamma in eight patients with colorectal cancer. Serum concentrations of sTNF-R and sICAM-1 increased significantly during the treatment period. Shedding of ICAM-1 and TNF-R induced by TNF-alpha and IFN-gamma could be responsible for the ineffectivity of TNF-alpha based treatment regimens.