The effect of the short-acting benzodiazepine lorazepam on motor cortex excitability was investigated in 11 healthy volunteers using the technique of focal transcranial magnetic stimulation. The threshold intensity for evoking an electromyographic response in the resting and active abductor digiti minimi muscle, the size of the motor evoked potential, the duration of the cortical and peripheral silent periods, the corticocortical inhibition and facilitation after paired magnetic stimuli, and the transcallosal inhibition were used as parameters to assess various aspects of motor system excitability. Baseline values were compared with data obtained 2, 5 and 24 h after a single oral dose of 2.5 mg lorazepam. Resting and active motor thresholds and the size of the motor evoked potential remained unchanged. The duration of the cortical silent period was prolonged with a maximum effect 5 h after drug intake, while the peripheral silent period did not show any lengthening at that time. The corticocortical inhibition showed a tendency toward more inhibition, while the corticocortical facilitation was almost completely suppressed. The transcallosal inhibition showed an inconsistent trend to less inhibition. In parallel to the pharmacokinetics of lorazepam, all effects peaked at 2 h and 5 h, and were (partially) reversible after 24 h. It is hypothesized that most of these findings are due to the reinforcement of GABA action by lorazepam at the level of the motor cortex. The lack of effect on motor threshold and on the size of the motor evoked potential may indicate that these parameters are physiologically distinct from corticocortical excitability and the cortical silent period. The relevance of the present data in clinical epileptology is discussed.