The basic paradigm for the induction of skin sensitization postulates chemical reactivity of a low-molecular-weight chemical, which leads to the formation of hapten-carrier conjugates composed of self-proteins covalently linked with the chemical. It is assumed that the immune system can specifically react to a small chemical in connection to a larger structure only, which is called the carrier. In almost all cases of skin sensitization this paradigm is valid, with the exception of heavy metals which can form stable coordinative bonds with proteins and thereby change their quaternary structure. In some cases a prohapten can be bioactivated and transformed into a hapten. This paradigm allows a search for structural alerts based on this chemical reactivity leading to hapten-carrier conjugates. The hapten concept can also be applied to some drug allergies, which are induced after oral administration of the drug like immune-mediated anemias and leukocytopenias. However, the same diseases...