We studied the effects of low frequency transcranial magnetic stimulation (TMS) on motor cortex excitability in humans. TMS at 0.1 Hz for one hour did not change cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used for induction of long term depression (LTD), led to a mean decrease in MEP amplitude of 19.5%. The decrease in cortical excitability lasted for at least 15 minutes after the end of 0.9 Hz stimulation. The mechanism underlying this decrease in excitability may be similar to LTD. TMS-induced reduction of cortical excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject which underlies the need for adequate monitoring even with stimulation at low frequencies.