Analysis of data on risk factors for the acute leukemias in adults continues, with a recent focus on myelodysplasia, a relatively common hematologic disorder of increasing importance among the elderly. Sometimes considered a preleukemic condition, myelodysplasia is associated with substantial morbidity and mortality, even in the absence of transformation to acute leukemia. We have completed a study of 158 adults with myelodysplasia and population controls and have found that, in contrast to acute myeloid leukemia patients who did not have an antecedent Myelodysplastic disorder, exposure to petroleum distillates, halogenated solvents, welding fumes and other agents was associated with substantially increased risk for disease. Differences between AML and myelodysplasia suggest that myelodysplasia may be a marker for chemical exposure in AML and that there are several pathways to disease. Using DNA samples that were available for 96 of the MDS patients, we explored differences in the frequency of specific polymorphisms in the glutathione S-transferases which may play a role in the metabolism of several known or suspected leukemogens. We found that persons with myelodysplasia were four times as likely to have the null genotype for GSTT1, consistent with the possibility that persons with this genotype have enhanced susceptibility to myelodysplasia, perhaps through decreased detoxification of environmental or endogenous carcinogens. We have nearly completed testing for ras mutations in bone marrow of 250 acute myeloid leukemia patients and will attempt to confirm a previous observation of an association between ras-positive leukemia and solvent exposure. We have also continued to analyze other aspects of our case- control study of risk factors for acute leukemia. Preliminary data suggest weak relationships between certain childhood infectious diseases and other immunologically mediated conditions and risk for specific subtypes of leukemia. A proposal is being developed to expand our work on myelodysplasia. Genetic and environmental factors will be studied among incident myelodysplasia and AML patients and population controls.