Hyperactivity of N-methyl-D-aspartate (NMDA) receptors may be one of the factors in the genesis of neuropathic pain. Ketamine is an NMDA-blocking agent widely used in human medicine. Ketamine (at 250 mcg/kg i.v. slow push) was administered to 6 patients for control of chronic neuropathic pain syndromes in double-blind placebo-controlled fashion. All 3 patients with peripheral nervous system (PNS) disease-related pain, and 2 of 3 patients with central pain and dysesthesia syndromes responded with a temporary decrease in the rating of ongoing pain. The allodynia, hyperalgesia and after-sensation present in 5 patients improved after the administration of ketamine. Dose-response estimation in 2 patients with PNS-related neuropathic pain revealed that ketamine was effective in dose-related fashion. Continuous subcutaneous infusion of ketamine administered to 1 patient with PNS-related neuropathic pain caused no additional improvement in pain control but caused intolerable cognitive and memory side effects. In contrast, side effects during single-dose injections were mild and well tolerated. Ketamine affected the evoked pain and associated after-sensation in chronic neuropathic pain syndromes more than the ongoing constant pain.