We studied the effects of lorazepam and dextromethorphan on the responses to 1 Hz repetitive transcranial magnetic stimulation applied to the left human motor cortex. Lorazepam, dextromethorphan or placebo was administered to 45 normal controls in a double-blind fashion 2.5 h before the repetitive transcranial magnetic stimulation procedure. Motor cortical excitability was measured with single transcranial magnetic stimulation pulses before and after 15 min of 1 Hz repetitive transcranial magnetic stimulation applied at supra-threshold intensity. 1 Hz repetitive transcranial magnetic stimulation resulted in a decrease in motor cortical excitability in the placebo group but not in the groups taking lorazepam or dextromethorphan. These results suggest that cortical responses to 1 Hz repetitive transcranial magnetic stimulation are dependent on activity at both gamma-aminobutyric acid and N-methyl-D-asparate receptor systems.