The aetiology of sporadic ALS is still unknown. Links with several environmental factors have been suggested, and some epidemiological studies have shown an increased incidence of ALS in rural populations. This study was designed to investigate risk exposures in a well-delimited rural population and to assess whether rural residency or occupations, such as farming, were associated with an increased risk of developing ALS. A prospective case-control-study of 108 sporadic ALS cases matched by age and sex to 122 controls was performed in Brittany from 2006 to 2008. A strong association was found between agricultural activity and ALS (odds ratio: 2.919; p = 0.01), while rural residence itself did not influence the risk of the disease. Bulbar forms of onset prevailed among agricultural workers as compared with other occupations (55 vs. 26%; p = 0.009). These results suggest a potential role of exposure to agricultural chemicals or contact with animals linked to agricultural work. The prevalence of bulbar forms of onset in agricultural workers has not been reported before. In addition to variable methodological approaches, differences in agricultural practices could explain the discrepancy between these findings and other studies.