We describe a patient with the acquired immunodeficiency syndrome who had persistent oral esophageal pseudomembranous candidiasis clinically refractory to nystatin, clotrimazole, and ketoconazole. In vitro resistance to clotrimazole was demonstrated as well. The patient received temporary relief with intravenous amphotericin B therapy, but this was associated with serious adverse effects, including transfusion-requiring anemia, azotemia, and severe thrombophlebitis. Despite two courses of intravenous amphotericin B therapy, the patient's highly symptomatic, recurrent oral and esophageal candidiasis continued. The patient was then treated with fluconazole and obtained immediate relief without associated adverse effects.