Adverse reactions to diphtheria and tetanus toxoids have frequently been reported. The cause of these reactions has been attributed to different factors, including sensitization by prior vaccination. However, this explanation does not hold for primary vaccination. In this case, undesirable reactions to diphtheria toxoid are most likely due to bacterial cellular fractions present in the vaccines. In fact, we were able to demonstrate that fortuitous contact with atoxigenic diphtheria strains can induce sensitization. Consequently, vaccination should be carried out with highly purified toxoids, so as to prevent untoward reactions due to the presence of impurities. It is also preferable to detoxify purified toxins, rather than to purify crude toxoids.