Objective: The aim of this study was to investigate the influence of psychosocial variables on patients with multiple sclerosis (MS) and the relationship between these variables and the onset of MS. Background: The current evidence indicates that many types of psychosocial factors are involved in the development and relapse of MS, and it has been suggested that they could serve as predictors as well. So far, little has been reported on the effect of psychosocial factors on MS and the relationship between psychosocial factors and the onset of MS. Methods: Forty-one patients, 15 males and 26 females, average age 37.44 ± 12.24 years (mean ± SD), were evaluated by the Life Event Scale, Eysenck Personality Questionnaire, Social Support Revaluate Scale and Symptom Check List 90 and compared with 41 equivalent healthy control subjects, 15 males and 26 females, average age 36.38 ± 12.84 years (mean ± SD). Disease, demographic, psychosocial and lifestyle factors were measured at baseline. Patients with MS were first diagnosed by 3 neurologists according to the Poser (1983) MS diagnostic criteria. Results: Significant differences were found between the MS and the control group in their negative emotions and symptoms such as depression, anxiety, obsession, phobia, tense interpersonal relationship and somatization disorder. Significant differences were found between the two groups in the total number of negative life events, their family problems and the utilization of social support. The scores for various negative emotions in the MS group correlated positively with those for neuroticisms in personality type, and negatively with those for introverted and extroverted personality. Many kinds of negative emotions in the MS group correlated positively with the total number of life events, negative life events and family problems. Many kinds of negative emotions in the MS group correlated negatively with the utilization of social support. Conclusion: The psychosocial factors are closely associated with MS onset and may play important roles in the development of the disease.