Despite the success of mass immunization in many countries, diphtheria cont
inues to play a major role as a potentially lethal resurgent infectious dis
ease. Early, accurate diagnosis is imperative since delay in specific thera
py may result in death. The microbiologic diagnosis of the disease, the ide
ntification of contacts and carriers, and the appropriate clinical manageme
nt of these patients are therefore crucial. The epidemiology of diseases ca
used by Corynebacterium diphtheriae has changed dramatically over the decad
es, a situation that is highlighted by the resurgence of infections in the
European region. These factors have strengthened the need for laboratories
to screen for C. diphtheriae. Many modified and new methodologies are now u
sed widely within laboratories for diphtheria diagnosis. Recent development
s have focused upon methods for detection of the lethal and potent exotoxin
produced by the causative organism, C. diphtheriae; this detection is the
definitive test for the microbiologic diagnosis of diphtheria.