BACKGROUND: Multiple sclerosis (MS) patients accumulate both physical and mental health problems along with disease progression. Valid and sensitive outcome measures are important to measure disease effects and the effect of treatment. OBJECTIVE: The objective of this study was to test the performance of the physical and mental summary scales of SF-36, SF-12, and RAND-36. METHODS: The scales were evaluated by comparing the scores of a cohort of 194 MS patients with general population data and using the Expanded Disability Status Scale (EDSS) and the Incapacity Status Scale-mental as criterion variables for physical functioning and mental health. RESULTS: All 3 physical summary scales were markedly reduced and correlated highly with the EDSS. The SF-36 mental summary score was only slightly reduced among MS patients (0.2 SD) compared with the general population, despite significantly reduced scores on all 4 health scales being most related to mental health and despite a high prevalence of mental health problems. This results from the poor physical functioning (mean scale score, 2.3 SD below the general population) and the orthogonal factor rotation used to derive independent measures of physical and mental health. Similar results were found for the SF-12. The nonorthogonal RAND-36 physical and mental summary scores were both markedly reduced. This is more compatible with the disease progression in MS and the results of the other measures of physical and mental health used in the study. CONCLUSIONS: The SF-36 and SF-12 mental health summary scales appear to overestimate mental health in people with MS.