The blood of normal C3H mice contains molecular factors that can rapidly lyse mammary carcinoma cells that enter the circulation. The cytotoxic effect of blood on tumor cells during incubation was most clearly demonstrated if fibrin formation was prevented. The conversion of the mammary carcinoma cells to ascites growth increased both the resistance to lysis in plasma and the ability to form lung colonies after intravenous injection. Mice that were surgically cured of numerous 9 mm tumors and survived for an average 10 months had a lower incidence (36%) of spontaneous metastases than mice that experienced one 30 mm tumor and survived for an average 8 weeks (65%). This is interpreted to mean that mice that retained their vitality by early surgical cures, could suppress the development of metastases by the action of normal serum factors that can destroy neoplastic cells that enter the circulation.