We evaluated 74 selected patients with amyotrophic lateral sclerosis (ALS) and 201 matched controls for risk factors for ALS by a case-control design and a sequential questionnaire/interview technique to quantitate biographic data. We analyzed occupational and recreational data only for 47 male patients and 47 corresponding patient controls; data for women were insufficient. We used nonparametric analyses to evaluate five primary comparisons of ALS patients with controls: (1) more hard physical labor, p not significant (NS); (2) greater frequency of neurodegenerative disease in family members, p NS; (3) greater exposure to lead, p less than 0.05; (4) more years lived in a rural community, p NS; and (5) more trauma or major surgery, p NS. Men with ALS had worked more frequently at blue-collar jobs (although not a statistically significant difference, p = 0.10) and at welding or soldering (p less than 0.01). These results suggest that there may be an association between ALS in men and exposure to lead vapor. The limited nature of the association favors a multifactorial etiologic mechanism of ALS.