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Sufficient evidence has accumulated in the last two years to indicate the importance of various drugs as etiological agents in the development of agranulocytosis. Although multiple factors are probably operative in a given case, it is apparent that the administration of a drug, usually amidopyrine, has frequently been the determining factor. First to suggest the possibility tnat certain drugs, particularly those containing a benzol ring, might be etiological agents was Kracke (1). Madison and Squier (2) presented the first cleancut clinical evidence indicating the relationship of a drug, usually amidopyrine, to the disease. These observations were followed by numerous clinical reports, all of them incriminating such drugs as arnidopyrine given either singly or in combination with barbiturates (allonal, peralga, etc.), phenacetin, arsphenamine, neo-arsphenamine, and dinitrophenol. Many of these reports were inconclusive, definite evidence for the drugdisease relationship being very scanty. Reznikoff (3), and more recently Jackson and Parker (4) examined the evidence for this relationship, and concluded that certain drugs undoubtedly played an important part in the causation of the disease, although the exact mechanism was unknown. Madison and Squier (2), Benjamin and Biederman (5), Sturgis and Isaacs (6), Rawls (7), Zinberg, Katzenstein, and Wise (8) and others were able to produce varying degrees of granulocytopenia by the administration of amidopyrine to patients who had recovered from the disease. All of these authors speculated regarding the mechanism of the ensuing granulocytopenia, and most of them concluded that some form of hypersensitivity to the drug was present. The present communication deals with the study of a group of four patients who recovered from the disease. In all of them a history of the use of amidopyrine prior to onset of

THE EFFECT OF DRUGS IN THE PRODUCTION OF AGRANULOCYTOSIS WITH PARTICULAR REFERENCE TO AMIDOPYRINE HYPERSENSITIVITY 1