Eight adult males were subjected to 40 hours of total sleep deprivation (TSD). Reaction time in a visual task and electroncephalographam (C3) were evaluated every 2 hours. One second of EEG before the stimuli was Fourier-transformed, and 750 ms after target and nontarget stimuli were averaged and visual event-related potentials (ERP) were obtained. Factorial analysis identified time windows that showed significant amplitude reduction and longer latencies with TSD: (1) 140 to 288 ms (P180-N242-P281); (2) 288 to 413 ms and 601 to 749 ms (N382; P718) and; (3) 531 to 601 ms (N500). Effect was strongest for N382 and P718, the amplitudes of which dropped to 20% of original size. The entire waveform recovered initial amplitudes and latencies after recovery sleep except for P718 latency. Waveforms within similar time intervals have been associated with attentional gating, sensory discrimination, target selection, uncertainty and decision processes. Amplitudes of the visual ERP were inversely correlated with hours of TSD, reaction time, and absolute power of the prestimulus EEG. Present results clearly show changes in fundamental neurophysiologic mechanisms as a result of TSD, indicating variability and reduction of the alertness mechanisms and changes in thalamocortical gating affecting attention, discrimination and decision-making.