It has been suggested that thalidomide may be effective in the management of Crohn's disease, including the associated oral lesions. We detail the clinical response to low-dose thalidomide of 5 patients with clinical features of orofacial granulomatosis or oral Crohn's disease recalcitrant to recognized immunosuppressant therapy. All patients had clinical resolution of their symptoms and signs. Transient somnolence was the only reported adverse effect. Remission was maintained by extending the period between thalidomide doses. Thalidomide should be considered an effective therapy for the short-term treatment of severe orofacial granulomatosis in appropriately counseled patients.