The cytostatic and cytolytic effects of the combination of Tumour Necrosis Factor (TNF) and Interferon-gamma (IFN-gamma) on freshly isolated, untransformed and non-tumorigenic mouse embryo fibroblast-like (MEF) as well as rat embryo fibroblast-like (REF) cells are reported. Both TNF and IFN-gamma decreased the proliferation rate of REF cells, and prolonged treatment with the combination of TNF and IFN-gamma was cytolytic to the cells. IFN-gamma alone also inhibited the growth of MEF cells, an activity not shared by TNF, and was even cytolytic after treatment for more than one week. Growth inhibition as well as cytolysis of MEF cells by IFN-gamma was strongly enhanced by TNF. This is one of the few reports regarding the cytotoxic action of the combination of recombinant TNF and IFN-gamma on untransformed cells.