Inhibition is of fundamental importance to regulate activity in cortical circuits. Inhibition is mediated through a diversity of different interneurones and gamma-aminobutyric acid A receptor (GABAAR) subtypes. Here we employed paired-pulse transcranial magnetic stimulation (TMS) to measure short interval intracortical inhibition (SICI), a GABAAR mediated inhibition in human motor cortex, to address the question which GABAAR subtype is responsible for this form of inhibition. It has been shown that classical benzodiazepines (diazepam, lorazepam) have a non-selective affinity profile at different -subunit bearing subtypes of the GABAAR while zolpidem has a 10fold greater affinity to the 1-subunit bearing GABAAR compared to those bearing the 2- or 3-subunit (Möhler et al., 2002; Möhler et al., 2004). We found that, in 7 healthy subjects, a single oral dose of 20 mg of diazepam or 2.5 mg of lorazepam significantly increased SICI, whereas 10 mg of zolpidem did not change SICI. This dissociation occurred despite equal sedation by all three drugs, an 1-subunit GABAAR mediated effect. The findings strongly suggest that SICI is not mediated by the 1-subunit bearing subtype of the GABAAR but by those bearing either the 2- or 3-subunit. This study represents an attempt by means of TMS to identify GABAAR subtype specific action at the systems level of human cortex, a highly relevant issue because the different -subunit bearing subtypes of the GABAAR are differently involved in benzodiazepine mediated effects such as sedation, amnesia or anxiolysis, in developmental cortical plasticity, and in neurological disorders such as epilepsy.