Objective: Multiple sclerosis (MS) is an incurable, chronic and unpredictable disease of the central nervous system. The purpose of this study was to investigate whether MS patients' illness representations impact on their adjustment to this debilitating illness even when controlling for the severity of their condition. Methods: One hundred and sixty-eight MS patients completed a questionnaire booklet comprised of the Illness Perceptions Questionnaire-Revised and a range of adjustment variables including the Sickness Impact Profile, the Fatigue Scale, the Hospital Anxiety and Depression Scale and the Rosenberg Self-Esteem Scale. The severity of patients' MS was measured by the type of MS, length of illness, remission status and ambulatory ability. Results: Hierarchical multiple regression analyses demonstrated that illness severity accounted for the majority of the variance in physical and role dysfunction, while patients' illness representations were the most significant predictors of levels of social dysfunction, fatigue, anxiety, depression and self-esteem. Conclusions: Patients' illness representations play a significant role in adjustment to MS. These results suggest that a psychological intervention, which addresses patients' illness representations, may assist in their adjustment to MS. (C) 2003 Elsevier Inc. All rights reserved.