Adverse reactions to antimicrobial agents consist of toxic effects mediated through chemical changes in tissue cells, sensitivity reactions produced by antigen-antibody reactions, and biological effects caused by alteration of the bacterial flora in the body. Patients vary in their susceptibility to these because of genetically determined differences in enzyme and protein make-up, differences in immunologic reactivity, differences in environment, or because of the effects of disease. Some antibiotics are capable of producing almost invariable damage to certain tissues if given long enough in sufficient dosage, whereas others produce disturbances in only occasional patients. Almost any organ in the body may be involved, indicating that the metabolic processes affected by these agents are represented to a varying degree in the cells of the host. Little is known of the specific mechanisms involved, but as information is acquired, it should be possible to reduce the incidence of reactions.