A recent report of a six-fold increase in prevalence of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, in soccer players prompted a similar investigation in National Football League players in the United States. Using the internet, a retrospective analysis indicated 8 of the 3,891 players who played or debuted after 1960 had ALS, a prevalence of 206 per 100,000, a 40-fold higher prevalence rate than the rate of 5 per 100,000 in the general U.S. population (p<.001, binomial theorem). While no etiology for ALS has been established, the very high rate associated with professional football warrants further examination.