The Social Security Administration (SSA) operates the world's largest and most stringent disability program, processing more than 3.5 million claims each year, with multiple sclerosis (MS) representing the third most common neurological diagnosis cited as the cause for disability. The purpose of this project is to determine whether current medical knowledge supports the SSA's stated policies regarding MS. The seven major research questions addressed during this review are as follows: Question 1a: What is the reliability of new McDonald criteria (incorporating supplementary information from radiologic and laboratory studies including magnetic resonance imaging MRI], visual evoked potential VEP], and cerebrospinal fluid CSF] analyses) compared with long-term follow-up diagnosis of clinically definite MS according to the Poser criteria? Question 1b: What is the inter-rater reliability of diagnosis of MS according to Poser or McDonald criteria among neurologists or between neurologists and non-neurologist physicians? Question 2: What clinical indicators, including particularly time-course of impairments, predict physical or mental impairment at 12 months? Question 3a: Among patients with MS, do current disease-modifying treatments result in long-term improvements in physical or mental outcomes compared to placebo or usual care? Question 3b: Among patients with MS, do treatments aimed at symptom management result in improvements in physical or mental outcomes compared to usual care? Question 4: Among individuals with MS, what physical, mental, laboratory, or radiographic findings have been associated with inability to work? Question 5: Among individuals with MS, how does elevated temperature or other environmental factors impair the capacity to work?