Although numerous studies have shown that brain-damaged patients tend to underestimate neuropsychological (NP) impairment when self-ratings are compared to informant ratings, the meaning of such discrepancies is not well studied in multiple sclerosis (MS). We compared patient self- and informant-report questionnaire ratings of NP functioning in 122 MS patients and 37 age- and education-matched normal controls. In addition to completing the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ), participants underwent NP testing and assessment of depression, personality, and neuropsychiatric symptoms. Based on the normal distribution of discrepancy scores, patients were classified according to whether they overestimated or underestimated their cognitive ability, relative to informant ratings. ANOVAs comparing test scores derived from overestimators, underestimators, and accurate estimators were significant for multiple measures of cognitive function, depression, personality, and neuropsychiatric symptoms. Overestimators were characterized by less depression and conscientiousness, and greater degrees of cognitive impairment, euphoric behavioral disinhibition, and unemployment as compared to underestimators. We conclude that patient/informant discrepancy scores on the MSNQ are associated with the aforementioned neuropsychiatric features, and that the MSNQ has potential utility for predicting euphoria and disinhibition syndromes in MS. (JINS, 2005, 11, 574–583.)All authors are from the State University of New York (SUNY) at Buffalo School of Medicine, Department of Neurology, Division of Departmental and Behavioral Neurosciences, and the Jacobs Neurological Institute, Buffalo General Hospital, Buffalo, NY.