Background and Aims: Intravenous lidocaine (IVL) produces analgesia in multiple painful disorders. The neurophysiological effects of IVL are not well defined, but studies in visceral nociceptive systems have shown that IVL has differential effects on subgroups of spinal neurons. The present study determined whether a similar differential effect of IVL occurs in spinal neurons excited by noxious cutaneous stimuli. Methods: In decerebrate, cervical spinal cord-transected rats, the lumbosacral spinal cord was exposed by a laminectomy. Single-unit recordings were made of dorsal horn neurons excited by noxious cutaneous stimuli. Each neuron's response to noxious (pinch) and nonnoxious (brush) cutaneous stimuli were determined and the effect of a counterirritation stimulus (noxious skin pinch presented in the upper body) on spontaneous activity quantified. In a subset of neurons, sequential doses of IVL were administered, and responses of each neuron to repeated 50°C heating of the hindpaw/tail were determined. Results: IVL dose-dependently inhibited neurons excited by heating of the hindpaw/tail. IVL produced significantly greater inhibition of both spontaneous and heat-evoked activity in neurons that did not show counterirritation effects when compared with those neurons that did show counterirritation effects. Standard classification of neurons as wide-dynamic range or nociceptive-specific was less predictive of the IVL effect. Conclusions: IVL had differential inhibitory effects on 2 spinal cutaneous nociceptive neuron populations. Other drugs could also have differential effects on sensory pathways, suggesting a mechanism whereby certain drugs differentially affect different types of pain. © 2006 American Society of Regional Anesthesia and Pain Medicine.