We studied the antitumor synergy of human recombinant tumor necrosis factor (TNF) in combination with recombinant interferon-r (IFN-r) both in vitro and in vivo. Synergistic cytotoxic effects were observed in all three of the human tumor cells lines examined. Binding assays of KB human nasopharynx carcinoma cell surface receptors for TNF revealed that IFN-r increased the number of receptors and suggest that this increase may play a key role in the synergism. Furthermore, a remarkable antitumor effect by TNF in combination with IFN-r was observed in nude mice implanted with KB cells. The results thus suggest that TNF and IFN-r in combination may provide the basis for a useful antitumor therapeutic regimen.