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We performed a case-control study of occupational and environmental risk factors in myelodysplastic syndromes (MDS) diagnosed at our institution, using the method of Siemiatycki. A control for each MDS case, matched for age, sex, and residence area was chosen. The questionnaire asked demographic data, medical history, and information on life-time environmental and occupational exposures. Occupational exposures were first assessed by job titles, then by evaluating exposure to a list of 70 chemicals, and the level and duration of exposure to those chemicals (exposure index). In the first 100 cases and controls analyzed, a significantly higher incidence of smokers or ex-smokers was seen in MDS cases (odds ratio, OR = 1.83, P = 0.03). A significant excess of MDS was found in male patients with jobs (or previous jobs) generally exposing to chemical compounds, including plant and machine operators and assemblers (odds ratio, OR = 3.73, P = 0.014) whereas, on the contrary, technicians and associate professionals were more often seen in controls (OR = 0.17, P = 0.002). In males, there was also a trend for more skilled agricultural workers and coal miners in MDS cases. In females, there was a non-significant trend for more professionals in controls. After adjusting for sex, age and smoking habits, significantly more frequent exposure to stone dusts (OR = 3.06, P = 0.011), and cereal dusts (OR = 2.27, P = 0.04) was found. There was also a trend for higher incidence of exposure to exhaust gases and nitro-organic explosives. In addition, significantly higher exposure indices to petrol and diesel derivatives (P = 0.03) and to fertilizers (P = 0.003) were seen in MDS cases, as compared to controls. No significant difference in exposure to other chemicals was seen between MDS cases and controls. These preliminary results of our study, which is accruing more cases, suggest, as two previously published case-control studies of risk factors in MDS, that exposure to some chemicals may be involved in the pathogenesis of MDS.