An open-label trial of clonidine, an a2-adrenergic agonist, was prescribed for patients with a clinical diagnosis of oral neuropathic pain or neuralgia involving the oral cavity. Clonidine (0.2 mg/g) was prepared in a cream base and applied four times daily to the site of pain. Seventeen patients were assessed: 10 were diagnosed with neuropathic pain, and 7 with neuralgia. Two of the 17 patients had complaints overlapping both neuropathic and neuralgic pain. In the patients with neuropathic pain, an overall mean reduction in severity of burning of 3% (on a 10-point visual analogue scale) was reported. Half of these patients reported clinical improvement; however, no patients reported complete resolution of symptoms. Of the patients with characteristics of neuralgia, 57% improved; and in those who reported improvement, a mean reduction of approximately 54% was reported. In the 4 patients with neuralgia who responded, a 94% reduction in pain was reported, with complete resolution of pain in 2 patients. This open-label clinical trial suggests that topical clonidine may be effective in the management of some patients with oral neuralgia-like pain, but may have a more limited effect in those paitents with oral neuropathic pain. Besides type of pain, no other variables predicted which of the patients would achieve pain reduction with topical clonidine. Although confirmation of cli nical efficacy requires double-blind clinical studies, this initial trial suggests that further study is warranted.