Forty-seven patients with relapsing-remitting (RR) or chronic-progressive (CP) multiple sclerosis (MS) were studied with a comprehensive battery of neuropsychological tests and measures of mood and fatigue. Group analyses revealed significant impairments in several cognitive domains in both RR and CP patients that persisted despite covariation for clinical features such as depression, fatigue, and disease duration. A discriminant analysis demonstrated that performance on the Symbol-Digit Modalities Test and the Paced Auditory Serial Addition Test, together with a measure of fatigue, accurately classified over two-thirds of control subjects, RR patients, and CP patients. We analyzed individual patient performance profiles in MS by converting raw scores to standard z-scores on the basis of age- and education-matched control subjects. Dementia was observed in a larger proportion of CP patients than RR patients, but cognitive impairments without dementia were as apparent among RR patients as CP patients. These findings confirm the presence of cognitive impairments in a carefully studied cohort of MS patients, demonstrate a procedure for characterizing statistically significant intellectual deficits in individual RR patients and CP patients, and underline the complex relationship between clinical features such as fatigue and cognitive difficulties in MS.