A few epidemiologic studies have suggested an association of agricultural work and pesticidesexposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis(ALS), though conflicting results have also been provided. We investigated through a populationbasedcase-control study the possible relation between overall occupational exposure to pesticidesand ALS risk in the northern Italy municipality of Reggio Emilia. By administering a questionnaire,we investigated occupational history and leisure-time habits of the 41 ALS patients diagnosed in the1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls. Morecases than controls were found to have been exposed to pesticides for at least six months (31.7% vs13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regressionmodel, we found an excess ALS risk associated with exposure to pesticides, with a relativerisk of 3.6 (95% confidence interval 1.2-10.5). Such association persisted after inclusion in the statisticalanalysis of potential confounders. Despite the limited statistical stability of the risk estimates,these results appear to indicate that occupational exposure to pesticides is a risk factor for ALS,suggesting the need to further investigate this issue