Peripheral afferent input provides critical drive for human motor control and motor learning. Stimulation of skin or deep muscle mechanoreceptors has been used to alter motor behaviour, both experimentally and therapeutically. While certain modalities, such as vibration, have attracted researchers for decades, central effects of mechanical pressure stimulation have been studied less frequently. This discrepancy is particularly striking given the limited understanding of physiological principles underlying common physiotherapeutic techniques that involve peripheral stimulation, such as reflex locomotion therapy (RLT). First, the thesis thoroughly reviews the current literature on central effects of pressure stimulation while contrasting it with some better understood examples of peripheral interventions, including vibration and muscle denervation using botulinum neurotoxin. Furthermore, results of four parallel investigations of central correlates of pressure stimulation are reported. Each study enrolled up to 30 young healthy individuals and was conducted according to single-blind randomised crossover design. The schedule consisted of two functional magnetic resonance imaging (fMRI), two paired-pulse transcranial magnetic stimulation (pTMS), or two heart rate variability (HRV) recording sessions. During each session, sustained manual pressure stimulation was delivered as an intervention, once at the right lateral heel according to RLT (active site), and once at the right lateral ankle (control site). FMRI data were acquired during the stimulation, as well as during performance of a sequential finger opposition motor task scheduled immediately before and after the intervention. Likewise, pTMS and HRV recordings were repeated before and after the stimulation. Statistical analyses evaluated differences between the active and control stimulation conditions. The fMRI results showed that stimulation at both sites evoked responses throughout the sensorimotor system that could be mostly separated into two anti-correlated networks of areas with transient positive or negative signal change and rapid adaptation. More sustained activation was only observed in the insulo-opercular cortices and pons during heel (active) stimulation. According to direct voxel-wise comparison, heel stimulation was also associated with significantly higher activation levels in the contralateral primary motor cortex and decreased activation in the posterior parietal cortex. In the second study, repeated motor performance was associated with extensive activation decreases regardless of stimulation site. However, stimulation of the heel specifically increased activation in the predominantly contralateral pontomedullary reticular formation and bilateral posterior cerebellum. On the other hand, heel stimulation reduced short-interval intracortical inhibition in the contralateral motor cortex in pTMS. Finally, spectral analysis of HRV yielded modest increases in vagal and sympathetic activity, but revealed no differences between stimulation sites. In conclusion, this thesis reviews literature on sensorimotor plasticity induced by modulation of the afferent input, highlights the limited amount of research devoted to peripheral pressure stimulation, and presents recently published original research providing evidence for site-specific differences in brain function. These include increased activation of the motor cortex as an immediate response to stimulation, as well as modulation of task-related activation in the hindbrain and decreased intracortical inhibition representing outlasting effects after extended stimulation. Finally, these results are proposed to reflect the behavioural effects of physiotherapeutic interventions previously observed in the clinical setting.