Tumour necrosis factors, TNF-α and TNF-β (previously called lymphotoxin), are the products of activated monocytes and lymphocytes, respectively, and both have recently been purified, sequenced and cloned by recombinant DNA methods^1–5, revealing 35% identity and 50% homology in the amino-acid sequence. Both proteins have been found to be specifically toxic to many tumour cells. Furthermore, it has been reported that various interferons are synergistic with TNF for anti-tumour effects in vitro^6–8, while activities attributed to the two proteins have also been shown to necrotize various tumours in vivo^2,3,9. We have now prepared ¹²⁵I-labelled highly purified recombinant human TNF-α to study in detail its binding to the human cervical carcinoma cell line ME-180. Our results indicate that there is a single class of specific high-affinity receptors for TNF on this cell line which has a K_d of about 0.2 nM and an average of 2,000 receptor sites per cell. The binding of labelled TNF-α to these cells can be inhibited by both TNF-α and TNF-β but not by γ-interferon (IFN-γ). However, preincubation of cells with IFN-γ increases the total number of TNF receptors two to threefold without any significant change in the affinity constant. This is the first report that TNF-α and -β share a common receptor and that the receptors can be up-regulated by interferon. Our results may explain previous observations regarding similar biological activities observed for these two cytotoxic proteins and also their synergistic action with interferons.