The primary somatosensory cortex (S1) in adult animals and humans is capable of rapid modification after deafferentation. These plastic changes may account for a loss of tonic control by nociceptive inputs over inhibitory mechanisms within structures of the dorsal column-medial lemniscal system. Most studies, however, have been performed under conditions where deafferentation of C and A delta fibres coexists with large-diameter fibres deafferentation. In this study the effect of the acute lesion of one ascending anterior lateral column on neuronal activity within the dorsal column-medial lemniscal system was assessed by recording somatosensory evoked potentials (SEPs) in seven patients who underwent unilateral percutaneous cervical cordotomy (PCC) as treatment for drug-resistant malignant pain.Spinal, brainstem and cortical SEPs were recorded 2h before and 3h after PCC by stimulating the posterior tibial nerve at both ankles. Amplitudes of cortical potentials obtained by stimulation of the leg contralateral to PCC were significantly increased after PCC. No significant changes in spinal or brainstem potentials were observed. PCC did not affect SEP components obtained by stimulation of the leg ipsilateral to PCC. Our results suggest that nociceptive deafferentation may induce a rapid modulation of cortical neuronal activity along the lemniscal pathway, thus providing the first evidence in humans of short-term cortical plasticity across the spinothalamic and lemniscal systems.