The prefrontal cortex has a crucial role in cognitive control, executive function and sensory processing. Functional imaging, neurophysiological and animal studies provide evidence for a functional connectivity between the dorsolateral prefrontal cortex (DFLPC) and the primary motor cortex (M1) during free choice but not instructed choice selection tasks. In this study, twin coil, neuronavigated transcranial magnetic stimulation (TMS) was used to examine the precise timing of the functional interaction between human left DLPFC and ipsilateral M1 during the execution of a free/specified choice-selection task involving the digits of the right hand. In a thumb muscle that was not involved in the task, a conditioning pulse to the left DLPFC enhanced the excitability of the ipsilateral M1 during free-selection more than specified selection 100 ms after presentation of the cue; the opposite effect was seen at 75 ms. However, the difference between free and externally specified conditions disappeared when a task specific muscle was investigated. In this case, the influence from DLPFC was dominated by task involvement rather than mode of selection, suggesting that other processes related to movement execution were also operating. Finally, we show that the effects were spatially specific since they were absent when an adjacent area of DLPFC was stimulated. These results reveal temporally and spatially selective interactions between BA46 and M1 that are both task and muscle specific.