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We report a case of oro-pharyngeal and oesophageal ulcerative disease in a AIDS patient. The patient complained of severe oral pain and dysphagia. Systemic manifestations as fever and fatigue were also present. Repeated microbiological exams were negative and therapy with either antibiotics or antiviral agents or corticosteroids or colchicine was unsuccessful. Thus, we started thalidomide: 200 mg/day X 21 days, followed by 100 mg/day X 25 days. A dramatic reduction of symptoms was observed within 15 days from the onset of treatment. The healing of ulcers was evident already one month after the start of therapy. No relevant side effects were reported. Among those patients with AIDS at low risk of side effects, thalidomide may represent a successful therapeutic presidium for severe ulcerative disease of the gastrointestinal tract.