Transmission usually occurs through intimate contact or by airborne respiratory droplets from asymptomatic carriers or convalescing patients. Many more people are asymptomatic carriers than contract active infection. Diphtheria is more prevalent during the colder months because of closer person-to-person indoor contact; however, infection may occur at any time during the year.

Thanks to effective immunization, diphtheria is rare in many parts of the world, including the United States. Since 1972, however, the incidence of cutaneous diphtheria has been increasing in the United States, especially in areas of the Pacific Northwest and the Southwest where crowding and poor hygienic conditions prevail. Most victims are children younger than age 15; about 10% of patients die as a result of the infection.

The extensive pseudomembrane formation and swelling that occur during the first few days of infection can cause respiratory obstruction. Other complications of diphtheria include myocarditis, polyneuritis (primarily affecting motor fibers but possibly also sensory neurons), encephalitis, cerebral infarction, bacteremia, renal failure, pulmonary emboli, and bronchopneumonia; these complications are caused by C. diphtheriae or other super-infecting organisms. Serum sickness may result from antitoxin therapy.

Most diphtheria infections go unrecognized, especially in partially immunized individuals. After an incubation period of less than a week, clinical cases of diphtheria characteristically show a thick, patchy, grayish green membrane over the mucous membranes of the pharynx, larynx, tonsils, soft palate, and nose as well as fever, sore throat, and crouplike symptoms such as a rasping cough, hoarseness, and the like. Attempts to remove the membrane usually cause bleeding, which is highly characteristic of diphtheria and distinguishes it from mononucleosis. If this membrane causes airway obstruction (particularly likely in laryngeal diphtheria), symptoms include tachypnea, stridor, possibly cyanosis, suprasternal retractions, and suffocation, if untreated. Adenopathy and cervical swelling can occur. In cutaneous diphtheria, skin lesions resemble impetigo. Symptoms of streptococcal pharyngitis and bacterial epiglottiditis are similar to those of diphtheria but are more acute in onset. With epiglottiditis, no membrane is evident on indirect laryngoscopy.