Stomatodynia is a difficult disease for both patients and clinicians. When facing true stomatodynia, i.e., idiopathic burning mouth, patients are offered poorly effective treatment. This open study reports the results of local application of clonazepam (0.5 or 1 mg) two or three times daily in 25 subjects who suffered from idiopathic stomatodynia. At the first evaluation, 4 weeks after the beginning of treatment, a visual analogue scale (VAS) that represented the intensity of pain decreased significantly from 6.2 +/- 0.3 to 3.0 +/- 0.5. At the second evaluation, 3 to 29 months after the first consultation, the VAS scores dropped significantly further to 2.6 +/- 0.5. Analysis of the individual results showed that 10 patients were totally cured and needed no further treatment, 6 patients had no benefit at all, and the remaining 9 patients had some improvement but were not considered to be cured since they did not wish to stop the treatment. Blood level tests that were performed 1 and 3 hours after the topical application revealed the presence of small amounts of the drug (3.3 ng/mL +/- 0.66 and 3.3 ng/mL +/- 0.52, respectively). The hypothesis that clonazepam acts locally to disrupt the neuropathologic mechanism that underlies stomatodynia is proposed. The risk factors that are recognized for this condition could decrease the density and/or ligand affinity of peripheral benzodiazepine receptors. This, in turn, could cause spontaneous pain from the tissues concerned.