Neuropathic pain is often severe, persistent, and responds poorly to analgesic medications. Recent evidence suggests that N-methyl-D-aspartate (NMDA) receptor antagonists may be effective in the treatment of neuropathic pain. The present trial was designed to test the efficacy of acute administration of the NMDA receptor antagonist amantadine in relieving surgical neuropathic pain in patients with cancer. The study sample consisted of 15 cancer patients with the diagnosis of surgical neuropathic pain. Two 500 ml infusions of either 200 mg amantadine or placebo were administered over a 3 h period, in a randomized order, 1 week apart from each other. Spontaneous and evoked pain were measured for 48 h before treatment, during treatment, and for 48 h following treatment. An average pain reduction of 85% was recorded at the end of amantadine infusion vs. 45% following placebo administration. The difference in pain relief between the two treatments was statistically significant (P = 0.009). Mean pain intensity remained significantly lower during the 48 h following amantadine treatment as compared with the 48 h prior to treatment (31% reduction; P = 0.006), whereas no such effect was found with the placebo (6% reduction; P = 0.40). Amantadine, but not the placebo, also reduced 'wind up' like pain (caused by repeated pinpricking) in four patients. We conclude that amantadine infusion is a safe and effective acute treatment for surgical neuropathic pain in cancer patients. Further trials with long-term oral or parenteral amantadine treatment should be conducted.