Summary It has been shown that mixtures of relatively large numbers of lymphoma cells and specific isoimmune serum fail to produce tumors when injected into compatible mice. The degree of neutralization is proportional to the amount of antiserum, provided that very large cell doses are not employed. In vitro incubation of serum-cell mixtures has no effect on the outcome of neutralization tests unless complement is present, in which case the level of neutralization observed is determined by the concentration of complement as well as the time of incubation. A striking enhancement of neutralization can be achieved by injecting the prospective hosts of the antiserum-cell mixtures intraperitoneally with guinea pig complement (0.25–1.0 ml/mouse). This treatment has no effect on the fate of grafts of tumor cells mixed with normal serum. Neutralization in the absence of exogenous complement is attributed to the action of host complement on antibody-sensitized tumor cells. Failure to demonstrate neutralization with large cell doses even when optimal amounts of antibody are present is ascribed to insufficient levels of host complement. The significance of these observations with respect to the mechanisms of homograft rejection and the so-called tumor inhibitory principle of guinea pig serum is discussed.