Single neuron activities responding to peripheral stimuli with short latencies were recorded within the thalamic nucleus ventralis posterolateralis (VPL) after transection of the spinothalamic tract (STT) in the cat under alpha-chloralose anesthesia. The VPL neurons showed spontaneous and evoked hyperactivity after STT transection, which was revealed at 1-2 weeks. The spontaneous hyperactivity further progressed until 3-4 weeks. These hyperactivities were observed in core-area neurons as well as neurons found in the shell area, suggesting that some, if not many, of the N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801, 4-16 mg; i.v.) attenuated both the spontaneous and evoked hyperactivity observed after STT transection. No such effects were demonstrated in sham-operated animals. These findings suggest that VPL neurons become hyperactive after STT transection through recruitment of NMDA receptors. The hyperactivity of VPL neurons may represent an important background process in the production of deafferentation pain induced by lesions involving the STT.