purpose: To evaluate the efficacy and safety of oral prednisone therapy for idiopathic esophageal ulcerations (IEU) associated with human immunodeficiency virus (HIV) infection. patients and methods: Over a 14-month period, all HIV-infected patients with IEU as defined by clinical, endoscopic, and pathologic criteria were prospectively identified. Prednisone was initiated at a dose of 40 mg/d orally, tapering 10 mg/wk, for a total of 1 month of therapy. Patients were closely followed to determine the response to therapy as well as the occurrence of any side effects related to prednisone. All patients were requested to undergo endoscopy within 1 week of the completion of therapy. results: Of 14 patients identified with IEU, 12 consented to prednisone therapy. The mean duration of esophageal symptoms was 2.9 weeks, and odynophagia was the most common presenting symptom. Ten of 12 patients had the acquired immunodeficiency syndrome. Eleven of the 12 patients (92%) had a complete symptomatic response, usually within the first week of therapy. In some patients, the response was dramatic such that oral intake could be rapidly resumed and discharge from the hospital possible. Two patients completed 2 and 3 weeks of therapy, respectively, prior to death, both with a complete symptomatic response. Endoscopic re-examination in seven patients demonstrated complete ulcer healing in all six symptomatic responders, but a persistent ulceration in the one nonresponder. The oral corticosteroid regimen was well tolerated. Mild asymptomatic Candida esophagitis was identified in three of seven patients undergoing follow-up endoscopy. One patient developed self-limited herpes zoster during therapy. No systemic opportunistic infections were documented during or within 1 month of the completion of therapy. conclusions: Oral corticosteroid therapy appears to be a highly efficacious and safe therapy for HIV-associated IEU. Further controlled studies will be necessary to conclusively establish efficacy, as well as determine the optimal dose and duration of therapy. © 1992.