The present study examined whether the excitability of the corticospinal pathway and the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the tonically contracting hand muscle are changed by tonic contraction of the adjacent hand muscle. The motor evoked potential (MEP) and cortical silent period (CSP) in the tonically contracting hand muscle were obtained while the adjacent hand muscle was either tonically contracting or at rest. The MEP and CSP of the first dorsal interosseous (FDI) muscle elicited across the scalp sites where the MEP is predominantly elicited in the FDI muscle were decreased by tonic contraction of the abductor digiti minimi (ADM) muscle. The centers of the area of the MEP and the duration of the CSP in the FDI muscle elicited across the sites where the MEP is predominantly elicited in the FDI muscle were lateral to those in the FDI muscle elicited across the sites where the MEP is elicited in both the FDI and ADM muscles. They were also lateral to those in the ADM muscle elicited either across the sites where the MEP is predominantly elicited in the ADM muscle, or across the sites where the MEP is elicited in both the FDI and ADM muscles. The decrease in the corticospinal excitability and the excitability of the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the FDI muscle may be due either to (1) the interaction between the activity of the lateral area of the FDI representation and the descending drive to the ADM muscle, or (2) the decreased susceptibility of the primary motor area that predominantly projects onto the corticospinal neurons in the FDI muscle, which also plays a role in independent finger movement when both the FDI and ADM muscles act together as synergists.