The inhibitory effects of 0.1 M EDTA on the lysis of E* [sheep erythrocytes (E) with at least 1 cell bound antigen-antibody complex and all the necessary complement (C) components for killing to occur] prepared by incubating EA [E-antibody] with whole GPC [guinea pig C] was studied. At high end point lysis (> 70%) 0.1 M EDTA failed to prevent Hb release, at lower end point, (< 60%) 0.1 M EDTA was effective. In all cases Hb release was inhibited by 25% BSA [bovine serum albumin]. When E* were prepared by incubating EAC1-8 with C9, similar results were obtained. In this system the difference in the ability of 0.1 M EDTA to inhibit Hb release at high or low end point lysis could not be correlated with the number of lesions/cell but appeared to be related to the C9 to SAC1-8 [the number of hemolytically effective sites on EAC1-8] ratio. With limiting SAC1-8 and excess C9, E* were produced from which Hb release could not be prevented by 0.1 M EDTA, whereas at lower C9 to SAC1-8 ratios Hb release was prevented by 0.1 M EDTA. These differences most probably reflect functionally different sized transmembrane channels that were produced at different C9 to SAC1-8 ratios.