Drug-induced adverse reactions, especially type B reactions, represent a major 
clinical problem. They also impart a significant degree of uncertainty into drug 
development because they are often not detected until the drug has been released 
onto the market. Type B reactions are also termed idiosyncratic drug reactions 
by many investigators due to their unpredictable nature and our lack of 
understanding of the mechanisms involved. It is currently believed that the 
majority of these reactions are immune-mediated and are caused by immunogenic 
conjugates formed from the reaction of a reactive metabolite of a drug with 
cellular proteins. It has been shown that most drugs associated with 
idiosyncratic reactions form reactive metabolites to some degree. Covalent 
binding of reactive metabolites to cellular proteins has also been shown in many 
cases. However, studies to reveal the role of reactive metabolites and their 
protein-adducts in the mechanism of drug-induced idiosyncratic reactions are 
lacking. This review will focus on our current understanding and speculative 
views on how a reactive metabolite of a drug might ultimately lead to 
immune-mediated toxicity.