The effect of storage on the susceptibility of sheep erythrocytes to complement-mediated lysis was examined systematically. Hemolysin titers of IgG and IgM anti-Forssman antibodies rose as cells were stored as did whole complement titers (CH50) of fresh human and guinea pig serum. The rise in titers was most marked during the first 8 days of storage. This rise was not explained by an inability of fresh cells to absorb complement-fixing antibody since the Cla fixation and transfer test demonstrated equal numbers of complement-fixing sites on cells of all ages. Cl titer was unaffected by length of cell storage but storage caused a marked increase in the titer of C4 and subsequent components in the complement sequence. The increased titer of C4 was not accompanied by an increase in the binding of C4 molecules to the cell membrane, and was due to an increase in the lytic efficiency of bound C4. One explanation for these observations is that location of membrane-bound complement components is critical in determining their ability to mediate cell lysis. Cell aging is associated with a loss of membrane substance and this offers more sites where membrane-bound complement may produce lysis.