The cause of sporadic amyotrophic lateral sclerosis (SALS) remains unknown. We attempted to find out if occupational exposure to toxicants plays a part in the pathogenesis of this disease. In an Australia-wide case-control study we compared the lifetime occupations of 611 SALS and 775 control individuals. Occupations were coded using country-specific as well as international classifications. The risk of SALS for each occupation was calculated with odds ratios using logistic regression. In addition, the literature was searched for possible toxicant links between our findings and previously-reported occupational associations with SALS. Male occupations in our study that required lower skills and tasks tended to have increased risks of SALS, and conversely, those occupations that required higher skills and tasks had decreased risks of SALS. Of all the occupations, only truck drivers, where exposure to diesel exhaust is common, maintained an increased risk of SALS throughout all occupational groups. Another large case-control study has also found truck drivers to be at risk of SALS, and almost two-thirds of occupations, as well as military duties, that have previously been associated with SALS have potential exposure to diesel exhaust. In conclusion, two of the largest case-control studies of SALS have now found that truck drivers have an increased risk of SALS. Since exposure to diesel exhaust is common in truck drivers, as well as in other occupations that have been linked to SALS, exposure to this toxicant may underlie some of the occupations that are associated with SALS.