Burning mouth syndrome (BMS) is a symptom complex involving pyrosis of tongue, palate, lips, buccal mucosa and/or esophagus which generally occurs in late adult life and commonly affects postmenopausal women. There is little if any pathology in oral cavity tissues; this has obscured understanding of the etiology of this syndrome. Whereas dentists are usually the first clinicians to evaluate these patients they are usually at a loss to treat them due to absence of any anatomical change in any oral cavity tissue. Similar frustrations occur among the various physicians to whom patients turn for evaluation and treatment. Many pragmatic therapies have been used to treat these patients, including hormones, antidepressants, hypnosis, acupuncture and psychotherapy, but all have been without success. We evaluated 53 patients with BMS, 42 women, 11 men, aged 20-84 y in an effort to discern its underlying etiology and apply appropriate therapy. To do this we obtained magnetic resonance spectroscopy (MRS) measurements of brain using a 2-dimensional J-PRESS sequence to evaluate gamma-aminobutyric acid (GABA), glutamic acid, N-acetyl aspartate, choline and creatine in various brain regions. Results indicated that only GABA levels were changed, particularly in the cingulate region, in which its concentration was decreased below normal. We then treated 46 patients in an open trial with a variety of GABAergic drugs and transcranial magnetic stimulation. These therapies inhibited or decreased pyrosis in 68% of these patients and using MRS studies we found increased brain GABA in the same regions in which it was found to be decreased before treatment. These results suggest that the etiology of BMS does not lie in any pathological change in oral cavity structures but rather in decreased brain GABA, which demonstrates that etiology of this syndrome lies in changes in a specific CNS inhibitory neurotransmitter. This concept is supported by results which indicated that GABAergic treatment both increased regional brain GABA and inhibited the pyrotic symptoms.