AbstractBackgroundPaired associative stimulation (PAS) is widely used to induce plasticity in the human motor cortex. Although reciprocal inhibition of antagonist muscles plays a fundamental role in human movements, change in cortical circuits for reciprocal muscles by PAS is unknown.MethodsWe investigated change in cortical plasticity for reciprocal muscles during PAS. PAS consisted of 200 pairs of peripheral electric stimulation of the right median nerve at the wrist at a frequency of 0.25 Hz followed by transcranial magnetic stimulation of the left M1 at the midpoint between the center of gravities of the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles. Measures of motor cortical excitability included resting motor threshold (RMT), GABAA‐mediated short‐interval intracortical inhibition (SICI), and GABAB‐mediated long‐interval intracortical inhibition (LICI).ResultsMotor evoked potential amplitude‐conditioned LICI for the FCR muscle was significantly decreased after PAS (P = 0.020), whereas that for the ECR muscle was significantly increased (P = 0.033). Changes in RMT and SICI for the FCR and ECR muscles were not significantly different before and after PAS. Corticospinal excitability for both reciprocal muscles was increased during PAS, but GABAB‐mediated cortical inhibitory functions for the agonist and antagonist muscles were reciprocally altered after PAS.ConclusionThese results implied that the cortical excitability for reciprocal muscles including GABAB‐ergic inhibitory systems within human M1 could be differently altered by PAS.