Hyperactivity of N-methyl D-aspartate (NMDA) receptors may be one of the factors in the maintenance of persistent stump and phantom limb pain. Ketamine (bolus at 0.1 mg/kg/5 min followed by an infusion of 7 micrograms/kg/min) was administered intravenously to 11 patients with established stump and phantom limb pain in a double-blind saline-controlled study. All 11 patients responded with a decrease in the rating of stump and phantom limb pain assessed by visual analogue scale (VAS) and McGill Pain Questionnaire (MPQ). Ketamine increased pressure-pain thresholds significantly. Wind-up like pain (pain evoked by repeatedly tapping the dysaesthetic skin area) was reduced significantly by ketamine. In contrast, no effect was seen on pain evoked by repeated thermal stimuli. Side effects were observed in nine patients. The results support the notion that stump and phantom pain are generated by activity in afferent fibres activated by mechanical but not by thermal stimuli and that the NMDA receptor is involved in the maintenance of postamputation pain states. NMDA receptor antagonists may have a potential in the treatment of stump and phantom limb pain.