Multiple sclerosis (MS) is a chronic debilitating disease that is associated with demyelination and axonal degeneration within the central nervous system. MS affects over 450,000 people in the United States. In Wisconsin there are over 11,000 people with MS, making it a highly prevalent disease. MS is a complex disease, in which environmental factors act together in a genetically susceptible person to cause disease. The goal of this exploratory project is to test the hypothesis that conditioning on genetic risk factors will assist in identifying the environmental trigger of MS. We will test our hypothesis using case-control association studies in unique data sets. These consist of 300 MS patients and 600 unrelated controls. All participants, including patients and controls, are born in Wisconsin, and they and their families have lived in the same region for several generations. Specifically, most patients had spent the putative critical exposure period in Wisconsin and most controls are selected from a population-based cohort. This study has three aims. (1) Complete recruitment of sporadic cases with MS, and healthy controls from Wisconsin. (2) Stratify the newly enrolled participants according to the presence or absence of the HLA- DRB1*1501 allele. (3) Compare the association between MS and two environmental risk factors, childhood infections and diet, in MS subjects who do and do not carry the DRB1*1501 allele. Multiple sclerosis (MS) is the most common neurological disease affecting young people of Northern European descent. MS is a complex disease, in which environmental factors trigger the onset of symptoms in persons who are genetically vulnerable to the disease. The goal of this study is to identify environmental triggers in patients known to carry the genetic susceptibility for MS. We believe that the study of the environmental trigger in a clinically and ethnically homogeneous study sample from the same geographic region will help identify these triggers. This in turn will allow disease control and prevention. [unreadable] [unreadable] [unreadable] [unreadable]