The initial step in interferon action consists of the binding to a specific high-affinity cell surface receptor. Mouse α and β interferon have been shown to share a common receptor. We now present evidence that mouse γ interferon does not compete for this receptor on mouse L 1210 and L 929 cells. Cholera toxin which binds specifically to the membrane monosialoganglioside GM1, and has been shown to inhibit interferon action, does not inhibit the specific binding of labeled mouse α/β interferon to L 1210 or L 929 cells. Conversely, mouse α/β interferon does not inhibit the specific binding of radioactive cholera toxin to L 929 cells. L 1210S cells which have a specific receptor for α/β interferon do not have a specific binding site for cholera toxin. We conclude from these studies that there is no evidence to indicate that cholera toxin and mouse α/β interferon share a common receptor.