Extracts of the membranes of normal red cells and red cells from all subpopulations of paroxysmal nocturnal (PNH) red cells inhibited antibody-mediated complement activation. These extracts were shown to accelerate decay of the complement complex. C42, and the relative amount of inhibitory activity was similar in normal and PNH membranes. Inhibitors derived from normal red cells markedly decreased lysis of both PNH and normal cells when antibody was present in excess and complement was limiting. These same inhibitors decreased PNH cell lysis to a much lesser degree when complement was activated with cobra venom or acidified serum. The susceptibility of the PNH cell to complement lysis because of an increased fixation of C3 to its membrane is not due to a difference in membrane-associated accelerator of the decay of the C42 complex.