The effect of sleep deprivation on human motor cortical excitability was investigated by evaluating the changes in motor evoked potentials from the thenar eminence muscles of the right hand in seven subjects. Motor threshold, motor evoked potential amplitude, silent period, intracortical inhibition, intracortical facilitation and F wave were studied. Recordings were performed every 6 h during the day-time (from 09.00 to 21.00 h) and every 3 h during the night-time (from 21.00 to 09.00 h). Significant increases in motor threshold, intracortical inhibition and silent period were noted in the recordings during the night associated with a return to baseline values in the morning. No significant changes were observed in any of the other parameters. Enhancement of intracortical motor inhibition is suggested to explain the effect of sleep deprivation.