Functional connections between dorsal premotor cortex (PMd) and primary motor cortex (M1) have been revealed by paired-pulse transcranial magnetic stimulation (TMS). We tested if such connections would be modulated during a cognitive process (response selection) known to rely on those circuits. PMd–M1 TMS applied 75 ms after a cue to select a manual response facilitated motor-evoked potentials (MEPs). MEPs were facilitated at 50 ms in a control task of response execution, suggesting that PMd–M1 interactions at 75 ms are functionally specific to the process of response selection. At 100 ms, PMd–M1 TMS delayed choice reaction time (RT). Importantly, the MEP (at 75 ms) and the RT (at 100 ms) effects were correlated in a way that was hand-specific. When the response was made with the M1-contralateral hand, MEPs correlated with slower RTs. When the response was made with the M1-ipsilateral hand, MEPs correlated with faster RTs. Paired-pulse TMS confined to M1 did not produce these effects, confirming the causal influence of PMd inputs. This study shows that a response selection signal evolves in PMd early during the reaction period (75–100 ms), impacts on M1 and affects behaviour. Such interactions are temporally, anatomically and functionally specific, and have a causal role in choosing which movement to make.