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To evaluate the efficacy of melaleuca oral solution in AIDS patients with fluconazole-resistant oropharyngeal candida infections.A prospective, single center, open-labeled study.A university-based inner-city HIV/AIDS clinic.Thirteen patients with AIDS and oral candidiasis documented to be clinically refractory to fluconazole, as defined by failure to respond to a minimum of 14 days of ≥ 400 mg fluconazole per day. Additionally, patients had in vitro resistance to fluconazole, defined by minimal inhibitory concentrations of ≥ 20 µg/ml.Patients were given 15 ml melaleuca oral solution four times daily to swish and expel for 2–4 weeks.Resolution of clinical lesions of oral pseudomembranous candidiasis lesions. Evaluations were performed weekly for 4 weeks and at the end of therapy for clinical signs of oral candidiasis. Quantitative yeast cultures were performed at each evaluation.A total of 13 patients were entered into the study, 12 were evaluable. At the 2-week evaluation, seven out of 12 patients had improved, none were cured, and six were unchanged. At the 4-week evaluation, eight out of 12 patients showed a response (two cured, six improved), four were non-responders, and one had deteriorated. A mycological response was seen in seven out of 12 patients. A followup evaluation 2–4 weeks after therapy was discontinued revealed that there were no clinical relapses in the two patients who were cured.Melaleuca oral solution appears to be effective as an alternative regimen for AIDS patients with oropharyngeal candidiasis refractory to fluconazole.