Eight cases of severe mucosal candidiasis in patients with AIDS who were taking fluconazole at a dosage of 400-800 mg/d are described. Candida albicans alone or in conjunction with Torulopsis glabrata or Candida stellatoidea was isolated from each patient. In vitro susceptibility testing demonstrated resistance to fluconazole in all eight cases. All tested isolates were susceptible to amphotericin B, and six of eight isolates tested were susceptible to itraconazole. All individuals were severely immunocompromised (CD4 lymphocyte counts: mean, 15/mm3; range, 6-39/mm3) and had been receiving prophylaxis with fluconazole for a mean of only 3 months (range, 1-7 months). The occurrence of candidal mucositis in patients receiving high doses of fluconazole is a matter of concern that requires further study in regard to the causes, prevention, and treatment of the disease.