Using the Neuropsychiatric Inventory (NPI), we studied euphoria and other behavioral changes in 75 consecutive, unselected multiple sclerosis (MS) patients and 25 healthy controls. We also assessed disease duration, clinical course, physical disability, personality, depression, insight, cognition, and caregiver distress. Factor analysis identified a cluster of symptoms--labeled euphoria/disinhibition--similar to the euphoria sclerotica syndrome originally described by Charcot and others. The euphoria/disinhibition factor score was elevated in 9% of patients and associated with secondary-progressive course, low agreeableness, poor insight, impaired cognition, and high caregiver distress. Thus, we used the NPI to validate the euphoria syndrome in multiple sclerosis (MS) and determined its frequency, and its neurological and psychological correlates.