These experiments investigated the role of a specific thalamic nucleus in the cellular response to noxious and non-noxious inputs. Single-unit extracellular responses to peripheral noxious stimuli were recorded with glass micropipettes in the nucleus parafascicularis (Pf) of the rat under chloral hydrate anesthesia. Bipolar stimulating/recording electrodes were inserted in the nucleus ventro-postero-lateralis (VPL) of the thalamus, in areas responsive to the peripheral noxious stimulation. Single-unit records in Pf and multi-unit records in VPL demonstrated that both these nuclei are differentially sensitive to noxious and non-noxious inputs: Pf was more sensitive to late (200-600 ms latency) high threshold noxious inputs, while VPL was more responsive to early (10-40 ms) low threshold non-noxious inputs. Late, high threshold inputs to VPL were selectively suppressed by systemic morphine and restored by naloxone. Trains of stimuli applied to VPL suppressed the response of 76% of Pf units, to peripheral noxious stimuli but did not inhibit the response of spinal cord dorsal horn units to the same stimuli. This inhibitory effect of VPL on Pf cells was not reversed by systemically administered naloxone. The neural pathways responsible for the VPL suppression of Pf nociception appear to be neither monosynaptic nor mediated through the spinal cord dorsal horn, nor through any single, naloxone-reversible, central opioid process. Nevertheless, this inhibitory effect of VPL stimulation on Pf nociception provides a physiological basis for the analgesic effects of thalamic stimulation on clinically observed deafferentation pain. It also supports the existence of a pain modulating system at the thalamic level comparable, at least in part, with the spinal Gate Control concept.