Multiple sclerosis (MS) is a disease of the central nervous system in which increased production of proinflammatory cytokines are associated with the pathogenic process of demyelination. MS patients frequently associate increased stress with periods of disease worsening or exacerbation. Increased levels of perceived stress result in an increase in the production of pro-inflammatory cytokines. Fluctuations in the production of proinflammatory cytokines have been shown to precede the development of MRI detectable cerebral lesions in individuals with MS. Stress may then directly contribute to pathologic lesion development worsening the course of MS through modulation of cytokine production. It is then critical to understand the relationships among: stress, cytokine production and MRI lesion. A pilot psychoneuroimmunologic investigation is proposed to investigate the level of CNS lesion burden as determined by quantification of MRI, cytokine production on the part of peripheral blood mononuclear cells and perceived stress in individuals with MS. 40 outpatients with MS will be examined at three time points: baseline, three months and nine months. Subjects will previously diagnosed with relapsing-remitting MS using the McDonald criteria. The cytokines chosen for analysis are believed involved in the pathogenesis of MS: tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-6, IL-10, and IL-12. The production of cytokines will be measured through the use of enzyme-linked immunoabsorbent assay (ELISA). Subjects will complete a series of standardized psychological instruments (the Perceived Stress Scale, the Profile of Mood States, the MS-Quality of Life Instrument, the Mishel Uncertainty in Illness Scale and the Jalowiec Coping Scale). An MRI of the brain will be performed with and without contrast. Prior to obtaining the MRI, a standard neurological examination will be performed and the Expanded Disability Status Scale completed. In addition, subjects will be asked to complete a self-report measure of disease symptomatology, the Multiple Sclerosis Symptom Checklist. Statistical analysis will utilize path analysis and repeated measures ANOVA. Clinically, the ability to correlate psychological factors with immunologic modulation and the appearance of lesions, can lead to the development of biobehavioral nursing interventions that could aid in alleviating perceived stress and symptomatology in those with MS.