['Fatigue is common and disabling in multiple sclerosis, yet its physiologic substrates remain poorly defined. The aim of this study was to determine the relationship between fatigue and an objective measure of alertness in MS patients.', 'This study enrolled 49 consecutive MS clinic patients at two academic hospitals in Toronto. Alertness was assessed with the psychomotor vigilance test (PVT), a ten-minute reaction-time test that measures attention and is sensitive to sleep loss. Patients with visual impairment or arm weakness were excluded. Validated tools were used to assess fatigue, disability, mood, and pain.', 'The average age was 43; 65% were women. Median EDSS was 2.0 (range 0-7.5). Fifty-five percent reported a high impact of fatigue on their lives. Psychomotor vigilance test performance was worse than in an age- and sex-matched population, with a mean reaction time of 315 msecs and 3.98 lapses >500 msec (p<0.001). In a multiple regression analysis, fatigue was the most significantly correlated factor with mean PVT reaction time (p<0.05), and disability was also significantly correlated (p<0.01). Mood and pain did not correlate with the PVT. Eighteen (37%) reported often experiencing restlessness in their legs at night.'] Is multiple sclerosis fatigue associated with reduced psychomotor vigilance?