We monitored 15 healthy young adults during 18 hours of sleep deprivation. Subjects were repeatedly tested on measures of the P300 (P3) event-related potential, reaction time, body temperature, and a subjective rating of fatigue. Statistically significant decreases in P3 amplitude (P < or = .01) and increases in P3 latency (P < or = .0001) were found during sleep deprivation. These changes correlated with body temperature and fatigue and were not due to circadian variation. Reaction time did not show a significant change over time. We conclude that the P3 potential is a more sensitive cognitive measure of sleep deprivation than reaction time, a measure commonly used in previous studies. We provide a review of the literature on the P3 and recommend the use of the P3 as a marker to examine sleep deprivation in health professionals.