In order to investigate the preparatory modulations of cortico-spinal excitability, reaction time (RT) methods were combined with transcranial magnetic stimulation (TMS) of the motor cortex. We analyzed the variations in the amplitude of motor potentials evoked in a prime mover (flexor digitorum sublimis) by TMS delivered during the foreperiod of a visual choice RT task. In experiment 1 (n = 10), the TMS was delivered either simultaneously with the warning signal or simultaneously with the response signal in two conditions of foreperiod duration: short (500 ms) and long (2500 ms). The peak amplitude of the motor evoked potentials diminished during the short foreperiod but not during the long foreperiod. Since RT was shorter when the foreperiod lasted 500 ms than when it lasted 2500 ms, this result suggests that the excitability of the cortico-spinal structures is minimal when the subject is optimally ready to react. In experiment 2 (n = 10), the time-course of this decrement was further explored. With this aim, only the short foreperiod was used and the TMS was delivered either 500 ms, 333 ms, 167 ms or 0 ms before the response signal. Cortico-spinal excitability decreased during the first 333 ms and then remained stable until the occurrence of the response signal. In light of previous studies, the present results suggest that the decrement of cortico-spinal excitability during the short foreperiod reflects an adaptative mechanism which increases the sensitivity of the motor structures to the forthcoming voluntary command.