The complex of multiple symptoms known as Gulf War Illness (GWI) continues to affect a substantial number of veterans who served in the 1990-1991 Gulf War. Despite considerable research, the biological processes underlying veterans symptoms have not been clearly elucidated. In order to develop useful diagnostic tests and optimize the search for effective GWI treatments, it is imperative to establish a more definitive and integrated understanding of the pathophysiology of this problem. This study utilizes a case-control design to evaluate diverse biological measures in a single, well-characterized and population-based sample of 130 Gulf War veterans residing in Central Texas. Eighty veterans with GWI are compared to 50 healthy veteran controls in a protocol that includes physical and neuropsychological evaluations, neuroimaging (MRI, fMRI, DTI), adrenal function tests, and diverse immune, inflammatory, and coagulation measures. Statistical analyses will determine which objective measures significantly distinguish GWI cases from controls, and explore the extent to which biological findings are interrelated and are associated with identifiable veteran subgroups. When complete, the study is expected to clarify many of the ambiguities currently associated with GWI and improve understanding of the biological processes that underlie veterans symptoms. This will facilitate efforts to identify useful diagnostic tests and promising treatments.