Background This study focuses on long-tenn mortality, specifically brain cancer, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and multiple sclerosis (MS) of 621,902 veterans who served in the 1990-1991 Persian Gulf War (GW), and 746,248 non-GW veterans. Methods Follow-up began with the date the veteran left the GW theater or May 1, 1991 and ended with the date of death or December 31, 2004. Cox proportional hazard models were used for analyses. Results Adjusted mortality rate ratios (aRR) of GW veterans compared to non-GW veterans were not statistically significant for brain cancer (aRR = 0.90, 95% confidence interval (0): 0.73, 1.11), MS (aRR=0.61, 95% CI: 0.23, 1.63), Parkinson's disease (aRR=0.71,95% CI:0.17,2.99),or ALS(aRR=0.96, 95% CI:0.56, 1.62). GW veterans potentially exposed to nerve agents for 2 or more days and GW veterans exposed to oil well fire smoke were at increased risk for brain cancer mortality (aRR = 2.71, 95% CI 1.25, 5.87; aRR = 1.81, 95% CI: 1.00, 3.27; respectively). Conclusions The risk of death due to ALS, MS, Parkinson's disease, and brain cancer was not associated with 1991 GW service in general. However, GW veterans potentially exposed to nerve agents at Khamisiyah, Iraq, and to oil well fire smoke had all increased risk of mortality due to brain cancer Am. J. Ind. Med. 52:663-670, 2009. (C) 2009 Wiley-Liss, Inc.