Dextromethorphan (100 mg, orally), an NMDA receptor antagonist, did not significantly attenuate pain intensity or unpleasantness induced by experimental ischemia or by topical capsaicin in healthy human subjects, nor did it increase the threshold for heat pain or mechanical pain. A dose of 200 mg produced marked side effects. Thus, systemically administered dextromethorphan does not attenuate pain at clinically applicable doses in humans.