Individuals that have fully recovered from diphtheria may continue to harbor the organisms in the throat or nose for weeks or even months. In the past, it was mainly through such healthy carriers that the disease was spread, and toxigenic bacteria were maintained in the population. Before mass immunization of children, carrier rates of C. diphtheriae of 5% or higher were observed.

Because of the high degree of susceptibility of children, artificial immunization at an early age is universally advocated. Toxoid is given in 2 or 3 doses (1 month apart) for primary immunization at an age of 3 - 4 months. A booster injection should be given about a year later, and it is advisable to administer several booster injections during childhood. Usually, infants in the United States are immunized with a trivalent vaccine containing diphtheria toxoid, pertussis vaccine, and tetanus toxoid (DPT or DTaP vaccine).

The relative absence of diphtheria in the United States is due primarily to the high level of appropriate immunization in children, and to an apparent reduction in toxin-producing strains of the bacterium. However, the increasing percentage of diphtheria cases in adults suggests that many adults may not be protected against diphtheria, because they have not received booster immunizations within the past ten years. A similar situation exists with tetanus.