Central to most hypotheses of the mechanism of idiosyncratic drug-induced blood 
dyscrasias is the involvement of reactive metabolites. In view of the reactive 
nature of the majority of such metabolites, it is likely that they are formed 
by, or in close proximity to the blood cells affected. The major oxidative 
system of neutrophils generates hypochlorous acid. We have demonstrated that the 
drugs associated with the highest incidence of agranulocytosis are oxidized to 
reactive metabolites by hypochlorous acid and/or activated neutrophils. There 
are many mechanisms by which such reactive metabolites could induce 
agranulocytosis. In the case of aminopyrine-induced agranulocytosis, most cases 
appear to involve drug-dependent anti-neutrophil antibodies, and these are 
likely to be induced by cell membrane antigens modified by the reactive 
metabolite of aminopyrine. The target of agranulocytosis associated with many 
other drugs is usually neutrophil precursors and may involve cytotoxicity or a 
cell-mediated immune reaction induced by a reactive metabolite. In the case of 
aplastic anaemia, there is evidence in some cases for involvement of cytotoxic T 
cells, which could either be induced by metabolites generated by neutrophils, or 
more likely, by reactive metabolites generated by stem cells.