In this prospective study, 96 healthy controls and 101 multiple sclerosis patients were followed up for as many as 6 years, and self-reported stressful events and health status were assessed. The authors evaluated (a) whether patients reported more stressful life events than healthy controls and (b) the bidirectional relationship between stress and functional deterioration among patients. Healthy controls reported more life events than patients, Odds ratio (OR) = 1.13, p < .0001; and this relationship was attributable to healthy controls' reporting more neutral/positive events than patients. A bidirectional relationship was confirmed between stress and illness: there was an increased risk of disease progression when rate of reported stressful events was higher, OR = 1.13, p < .0003, and an increased risk of reported stressful events when rate of disease progression was higher, OR = 2.13, p < .0001. There were no differences in reported stress by level of baseline disability. The authors concluded that multiple sclerosis patients demonstrate a vicious cycle between stress and disease progression.