Recent observations indicate that a number of adverse drug reactions affecting the human erythrocyte proceed by immune mechanisms. Such immune reactions are recognized and studied by the Coombs' antiglobulin test. Three patients are described who represent examples of immune injury to red cells by three different processes involving chemically unrelated drugs. The mechanisms of induction of the positive Coombs' test are  the hapten type, associated with high-dose penicillin therapy, resulting in a positive anti-gamma Coombs' test;  the "innocent bystander" reaction, seen after quinine administration, which is associated with an anti-complement antiglobulin test; and  the alpha-methyldopa type, in which anti-gamma reactions are seen. The clinical characteristics and the distinguishing serologic features of each type of red cell-protein interaction are described.
When erythrocytes are sensitized by antibody or complement or both, certain in vivo events may occur that lead to premature destruction of such cells. Erythrophagocytosis, fragmentation, and spherocytosis may result from the interaction of reticuloendothelial cells with antibody-coated erythrocytes, and the consequences of these interactions are discussed.