The killing or lysis of nucleated cells, erythrocytes, bacteria, and other targets (e.g., liposomes) by antibody and complement is the result of complex series of actions and interactions between antibody, components of the complement system, and the cell. The complement attack mechanism has strict qualitative and quantitative requirements. For efficient activity, sufficient amounts of antibody must bind to the cell, the antibody must be of the complement-fixing type, and sufficient amounts of complement components must be activated and fixed to the surface of the target cells. Nucleated cells of different types differ in their sensitivity to the cytotoxic action of complement. This difference in sensitivity may be attributed to differences in metabolic properties and/or the chemical and physical composition of the cells. Since complement action occurs primarily on or in the cell membrane, the properties of the cell which may affect the outcome of complement-mediated attack should be linked to cell membrane function and integrity. The relationship between the susceptibility of nucleated cells to complement-mediated killing and the chemical and metabolic properties of the cells will be discussed in this review.