Oral recurrent aphthous ulceration (RAU) is a well-recognized complication in patients infected with human immunodeficiency virus. RAU can be progressive and destructive, causing dysphagia and secondary malnutrition. The aetiology of RAU remains unknown, and its response to available treatments is often unsatisfactory. We describe three patients with advanced AIDS who suffered from extensive RAU which failed to respond to several treatments, including topical viscous lidocaine and topical and systemic glucocorticoids. Owing to difficulties in using thalidomide (two patients had neurological conditions which precluded thalidomide use), all three patients were treated with an oral solution containing recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 400 μg in 5% glucose 200 mL). From the first application, all three patients showed significant improvement of their lesions and amelioration of pain, and they were completely cured in a few days. No adverse effects were recorded. The patients did not show relapses of RAU over a prolonged follow-up. Controlled trials are warranted in order to establish the role of GM-CSF as a valid, alternative option for aphthous ulcerations of the mouth in AIDS patients in whom corticosteroids or thalidomide are not suitable.