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Since the beginning of the AIDS epidemic, mucocutaneous candidiasis has been the most common opportunistic disorder associated with HIV infection. Oral and esophageal candidiasis remains a significant problem among HIV-infected individuals, even in the era of effective antiretroviral therapy, particularly at advanced stages of immune deficiency. As a result of the widespread use of oral azole compounds, increasing rates of resistance to fluconazole and itraconazole have been observed among Candida albicans isolates [1–3]. Amphotericin B given as an oral suspension has yielded disappointing results [4], and long-term systemic therapy with this potent agent is associated with a high incidence of renal side-effects as well as the hazards of chronic indwelling intravenous catheters. For these reasons, an increasing number of individuals are reaching the end of acceptable, proven options for oral and esophageal candidiasis, a disorder that can have a dramatic impact on nutrition, adherence to medication regimens and quality of life. Salivary flow and composition plays an important role in local defense of the mucous membranes of the mouth against Candida[5]. Lactoferrin, an iron-binding protein normally present in human saliva, can be deficient in HIV-infected individuals, especially those with significant oral candidiasis [6]. Bovine lactoferrin, which exerts its antimicrobial effect by depriving organisms of iron, has been shown to be fungicidal to C. albicans and Candida krusei in vitro[7] and to inhibit hyphal growth in various candidal species [8], including azole-resistant strains of C. albicans[9], and may act synergistically with azole compounds [10] and enhance the fungistatic effect of neutrophils [11]. Lysozyme, another constituent of saliva, also inhibits a variety of Candida species [12] and may also act synergistically with certain azole antifungal drugs [13]. For these reasons, a commercial mouthwash containing bovine lactoferrin as well as lysozyme was felt to represent a potential therapeutic option for a female patient with advanced HIV infection, suffering from extensive oral candidiasis despite prolonged systemic therapy with amphotericin B and azole compounds. A 36-year-old Caucasian woman diagnosed with HIV infection in 1990 first presented with oral candidiasis in 1995 for which she was treated with oral fluconazole. After approximately 2 years of intermittent therapy, the patient developed progressive, severe oral candidiasis that no longer responded to fluconazole even at high oral doses administered daily. Oral itraconazole and oral amphotericin B suspension were also ineffective at controlling the infection. Intravenous amphotericin B three times a week was instituted in August 1997 and resulted in a nearly complete response that lasted until November 1999, when progressive oral and esophageal candidiasis recurred and did not respond to daily amphotericin B. This therapy was discontinued in December 1999 because of its ineffectiveness and severe renal tubular acidosis, and oral itraconazole was reinstituted at a dose of 200 mg twice a day. Oral and esophageal candidiasis became increasingly more severe and the patient became progressively anorectic with nausea and frequent daily vomiting. Daily granulocyte stimulating factor was administered and the thrush improved for several weeks, but eventually progressed and the therapy was discontinued. Over the following 4 months, the patient's weight decreased from 90 to 73 lb. On 1 May 2000, with extensive oral candidiasis involving the palate, buccal mucosa, tongue and upper and lower gingival surfaces, she began therapy with lactoferrin- and lysozyme-containing mouthwash. She was instructed to swish and gargle without swallowing for 30 s twice after each meal and continued itraconazole. After 10 days of this therapy, her appetite improved dramatically and her weight increased from 73 to 80 lb. After an additional 21 days, the oral candidiasis had resolved completely, as had the anorexia, nausea and vomiting. The prompt, complete resolution of severe oral candidiasis after 5 years of incomplete response to fluconazole, itraconazole, topical and systemic amphotericin B and granulocyte colony-stimulating factor was temporally associated with the institution of therapy with lactoferrin- and lysozyme-containing mouthwash and the continuation of itraconazole. No improvement in viral load or immune function had preceded or coincided with the resolution of candidiasis. Between 1996 and 2000, the patient had received a variety of combination antiretroviral regimens, all with incomplete viral suppression, the viral load never falling below 32 000 copies/mm3. The CD4 lymphocyte count did not rise above 10/mm3 after 1997. The rapidity of response of her candidal infection suggests a direct effect of the mouthwash on the organism. The commercial mouthwash used, Biotene (Laclede Inc., Rancho Dominguez, California) contains lysozyme and bovine lactoferrin. It is unknown what the relative contribution of these proteins was to the therapeutic effect seen in this patient. This case suggests that lactoferrin- or lysozyme-containing compounds may represent an alternative or adjunct to systemic antifungal agents in the therapy of oral candidiasis in HIV-infected patients. Joseph R. Masci