While searching for lymphocyte surface antigens in mouse saliva, we have observed that this secretion prevented the cmediated lysis of lymphocytes in a microlymphocytoxicity test (Terasaki plate). Mouse saliva has a preferential action on the C3 and C5 molecule which are degraded within 1 min in whole human serum, and then acts later on C2 and C4. Mouse saliva has no action on C1 and late components C6 to C9. With purified components the kinetic action of mouse saliva is slowed down. The action of saliva is inhibited by PMSF, TCLK, and aprotinine which indicates the role of a tryptic-like enzyme. When mouse saliva is injected i.v. into rats, the hemolytic capacity of their C is completely abolished in the first 24 hr and then recovers to its normal level on the 3rd day after injection. This inhibition of the C reaction is also obtained with rat and rabbit saliva but never with any of the human saliva tested.