During voluntary motor acts, potential perturbations due to transient external forces are counteracted very quickly by short- and long-latency stretch reflexes (SLSR and LLSR, respectively). The LLSR, presumably linked to a transcortical loop, can be modulated by the subjects' intention. Here, we used combined TMS-EEG to study cortical mechanisms involved in this intention-related modulation both before and during the reaction to a mechanical perturbation. Subjects had to prepare for a brisk wrist extension under the instruction either to 'resist' the perturbation or to 'let-go'. Following the perturbation, the early cortical evoked activity (45-75. ms) was greater in the 'let-go' condition; moreover, its amplitude was negatively correlated with the LLSR amplitude, regardless of condition. After 100. ms the pattern reversed, the late evoked activity (presumably linked to the voluntary reaction) was greater in the 'resist' condition. The early and late evoked activities also differed in their topography. Therefore, the cortical mechanisms involved in the intention-related LLSR modulation differ from those involved in the voluntary reaction. In addition, in response to a single-pulse TMS delivered during the expectation of the mechanical perturbation, the TMS-evoked N100 amplitude decreased when subjects intended to 'let-go', suggesting anticipatory decreased activity of intracortical inhibitory sensorimotor networks. Taken together, these results support the idea that anticipatory processes preset the sensorimotor cortex so as to adapt its early reaction to the perturbation relative to the subjects' intention. ?? 2010 Elsevier Inc.