The possibility that C’3 participates in tumor rejection was investigated in DBA/2 mice previously immunized against L1210 leukemia and in Swiss mice previously immunized against Ehrlich’s adenocarcinoma. In both the cases, animals treated with an appropriate dose of cobra venom factor to produce a C’3 depletion for some days after the tumor challenge, developed the neoplasia and had a mortality rate analogous to that of non-immunized animals. Studies on the peritoneal washing cells obtained at different times after the challenge revealed that in C’3 depleted immunized mice IgM are present on lymphocytes, macrophages and tumor cells, as in the immunized controls, but no contact between the cells and no macrophage phagocytosis were observed and the number of tumor cells increased progressively. These findings indicate that C’3 is critically involved in the rejection of the experimental tumors c