Suppressor of cytokine signaling (SOCS)-1 is a critical inhibitor of IFN-γ signal transduction in vivo, but the precise biochemical mechanism of action of SOCS-1 is unclear. Studies in vitro have shown that SOCS-1 binds to Jaks and inhibits their catalytic activity, but recent studies indicate SOCS-1 may act in a similar manner to SOCS-3 by firstly interacting with cytokine receptors and then inhibiting Jak activity. Here, we have generated mice, termed Ifngr1 441F, in which a putative SOCS-1 binding site, tyrosine 441 (Y441), on the IFN-γ receptor subunit 1 (IFNGR1) is mutated. We confirm that SOCS-1 binds to IFNGR1 in wild-type but not mutant cells. Mutation of Y441 results in impaired negative regulation of IFN-γ signaling. IFN-γ-induced STAT1 activation is prolonged in Ifngr1 441F cells, but not to the extent seen in cells completely lacking SOCS-1, suggesting that SOCS-1 maintains activity to modulate IFN-γ signaling via other mechanisms. Despite this, we show that hypersensitivity to IFN-γ results in enhanced innate tumor protection in Ifngr1 441F mice in vivo, and unregulated expression of an IFN-γ–dependent chemokine, monokine-induced by IFN-γ. Collectively, these data indicate that Y441 contributes to the regulation of signaling through IFNGR1 via the recruitment of SOCS-1 to the receptor.