The general objective of the proposed research is to explore and quantify the role of drugs and other factors in the etiology of agranulocytosis and aplastic anemia, using an existing database. The data were collected in the International Agranulocytosis and Aplastic Anemia Study (IAAAS), a multicenter population-based case- control study conducted from 1980 to 1986 in eight regions. The study was funded by a pharmaceutical company, at a cost of $10 million, to investigate a single hypothesis, but information was obtained on all drugs and on other factors, enabling a general investigation of the etiology of the dyscrasias. The database contains 319 cases of agranulocytosis, 152 of aplastic anemia, and 2180 hospital controls. This proposal is for data analysis only. Standard case-control methods will be used. In most instances multivariate analysis will be used to control confounding, especially by simultaneous use of other causal drugs. Adverse effects and the relative safety of drugs in relation to the two dyscrasias will be documented. Because the IAAAS is population-based, incidence rates are provided directly, and excess risks (absolute risks) will be estimated for associated drugs. Such quantitative measures of association are generally unavailable. Among the drugs that will be analyzed are various categories such as psychotropics, antihistamines, and cardiovascular drugs, and individual drugs such as allopurinol. Factors other than drugs will also be evaluated, including exposure to radiation and chemicals such as benzene and insecticides, history of viral infection, and history of allergy and other conditions. Major findings will be published in individual papers. In addition, a monograph describing the methods, all of the results, and the conclusions of the IAAAS will be prepared. The database contains the largest series of cases of agranulocytosis and aplastic anemia ever assembled. It is not likely that such a large-scale and expensive study of these outcomes will be conducted again. The proposed grant will enable the full scientific and public health benefits to be obtained from this unique resource, st a modest incremental cost.