Cytolyis induced by the activated complement sequence and lysis of cells in hypotonic solution have many common characteristics. The demonstration of whether or not the functional complement lesion is identical to the membrane lesion produced in hypotonic lysis would seem a basic step in elucidating the mechanism of complement action. We evaluated the equivalence of the two membrane lesions by asking whether complement-impaired and hypotonically-damaged membranes reseal (i.e., regain selective solute permeability) under the same conditions. Osmotically lysed ghosts were prepared by suspending sheep erythrocytes in hypotonic sodium phosphate. Complement-lysed ghosts were prepared either by treating sensitized ghosts with human serum or by treating sensitized erythrocytes with serum and collecting the lysed cells. Resealing was induced by incubating ghosts in phosphate-buffered sodium chloride for 45 min at 37°C. By virtue of their ability to retain solutes and, hence, intracellular water, resealed ghosts possess buoyancy when centrifuged.