The findings of recent studies have suggested that nucleus submedius (Sm) may be an important thalamic relay for nociceptive information. The aim of the present electrophysiological study was to examine in greater detail the activity and response properties of neurons in the rat Sm in order to further evaluate this hypothesis. Single unit extracellular recordings from neurons histologically verified to be in Sm were obtained in urethane/chloralose-anesthetized rats. Noxious but not innocuous mechanical stimulation elicited responses in 75% of the 204 neurons studied. Most (85%) of these neurons were excited, 10% were inhibited and a few neurons (5%) were excited by stimulation at some sites on the body and inhibited from other sites. The receptive fields were usually very large and bilateral. No marked differences were observed in the incidence, response type, or spontaneous activity of neurons located in dorsal, ventral, rostral or caudal parts of Sm. Most of these neurons (99 of 108, 92%) also responded to noxious heating and had a mean threshold of 47°C. The majority of the neurons (19 of 21, 90%) also responded to subcutaneous, intramuscular or intraperitoneal injections of noxious chemicals (formalin or hypertonic saline). The responses elicited by pinching skin or squeezing muscle were frequently facilitated by the subcutaneous or intramuscular injections of formalin. Single electrical stimuli delivered to the cutaneous receptive field rarely produced responses. However, short trains (15–25 msec trains of 200 Hz, 3 msec pulses at 5–10 mA) delivered repetitively elicited responses in 90% (n = 73) of the neurons. These responses appearing after repetitive stimulation frequently resembled the ‘wind-up’ pattern observed in spinal cord dorsal horn. The conduction velocities of the primary afferents which elicited the Sm neuronal responses as estimated from the latency differences of responses elicited by stimulation at two points along the tail, were indicative of recruitment of Aδ and C fibers. These findings provide further support for the proposed role of Sm in thalamic nociceptive mechanisms.