This population-based case-control study was conducted in three countries in western Washington State to evaluate associations between workplace exposures and the risk of amyotrophic lateral sclerosis (ALS). Cases (n = 174) were all newly diagnosed with ALS by neurologists during 1990-1994, and controls (n = 348), who were matched according to age (+/-5 years) and sex, were identified via random-digit dialing or Medicare enrollment files. Four industrial hygienists blindly assessed detailed lifetime job histories for exposures to metals, solvents, and agricultural chemicals. Case-control comparisons were made for jobs held between 15 years of age and 10 years prior to the cases' dates of diagnosis. After adjustment for age and education, ever exposure to agricultural chemicals was associated with ALS (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.1-3.5); this association was observed separately in men (OR = 2.4, 95% CI 1.2-4.8) but not in women (OR = 0.9, 95% CI 0.2-3.8). Among men, the odds ratio for low exposure to agricultural chemicals (below the median level for exposed controls) relative to no exposure was 1.5 (95% CI 0.4-5.3), and for high exposure, it was 2.8 (95% CI 1.3-6.1) (p for trend = 0.03). Similar analyses based on the panel's assessment of exposures to metals and solvents showed no associations. These findings suggest an association between ALS and agricultural chemicals in men.