Optimal conditions for the killing of normal human lymphocytes by IgG antibody and autologous normal human serum were established. When serum from a patient with acute lymphoblastic leukemia was used in place of the normal serum, the rate and extent of killing was markedly reduced. Levels of all complement components were equivalent in the normal and leukemic sera. Furthermore, if the patient's serum was mixed with normal serum, killing was inhibited at concentrations of the patient's serum of 25% or more. A purified preparation of a C3 inhibitor, previously demonstrated to occur in these patients, had a similar effect when mixed with normal serum. In addition, sensitized target cells incubated with this inhibitor and normal serum remained viable after washing and reexposure to fresh serum. If, however, the inhibitor was added to the sensitized cells in the absence of serum and then removed, killing proceeded normally on the subsequent addition of normal serum. Finally, the inhibitor was able to be eluted from sensitized target cells exposed to the inhibitor in the presence of serum. It would appear, therefore, that the inhibitor fixes to a sensitized cell in the presence of complement yielding a target cell that is resistant to the cytotoxic activity of complement. The fact that the inhibitor may also be eluted from cells obtained from the bone marrow of patients with acute lymphoblastic leukemia when the tumor burden is high suggests that a similar process may also occur in vivo.