BACKGROUND: Dextromethorphan (DEX) is an NMDA receptor antagonist which has recently been introduced for the treatment of chronic pain mainly to reduce the central sensitization component of pain. It is also reported to reduce the pain from acute ischemia of an extremity in a rat model which has a similar mechanism as tourniquet pain. The purpose of this experiment was to see if dextromethorphan could reduce tourniquet pain in normal volunteers. METHODS: A double blind randomized cross-over test was done on ten healthy male volunteers. Each subject was orally administered with three different doses of DEX (placebo, 30, 60 mg) 1 h before the study according to a preallocated randomized table. The subject was not reallocated for the test within two weeks of the previous test. After a 10 minute acclimation period before each test, the degree of tourniquet pain measured by VAS, arterial blood pressure, heart rate, respiration rate, and pressure-evoked pain were measured before and every 5 minutes after inflation of the tourniquet until the subject felt unbearable pain. A mixed model for repeated measurement of data was used for statistical analysis (P < 0.05). RESULTS: There was no statistical difference between different doses of DEX including the placebo. Rather, there was a tendency that DEX increases the pain. And there also was a tendency that average time to reach unbearable pain was decreased by DEX (P > 0.05). CONCLUSIONS: DEX is not effective in controlling tourniquet pain in normal awake subjects.