OBJECTIVES: Fluconazole-resistant oropharyngeal candidiasis (OPC) is a rapidly growing problem in HIV-infected patients. To better understand the pathogenesis of fluconazole resistance in this setting, asymptomatic candidal carriage was determined by means of oral swabs regularly performed in all patients without clinical signs of OPC seen at our HIV outpatient clinic. Controls were 204 asymptomatic healthcare workers without previous exposure to fluconazole. METHODS: Swabs were plated on three solid media and put in a Sabouraud broth. Phenotypically different colonies were identified to the species level. Susceptibility to fluconazole was determined using a disk diffusion test with 50 microg fluconazole disks on yeast nitrogen agar, with a cut-off value of 25 mm. RESULTS: Swabs were performed in 538 consecutive HIV-positive patients, of whom 216 (40%) had had prior episode(s) of OPC and/or were previously exposed to fluconazole. Yeasts were grown in 418/538 HIV-positive patients (78%), compared to 57/204 controls (28%) (p < 0.05). In HIV-positive patients, yeasts were grown in 189/216 (88%) of those with past fluconazole exposure, and in 229/322 (71%) without exposure (p < 0.05). A total of 589 isolates were grown in the 538 HIV-positive patients (451 C. albicans, 88 C. glabrata, 22 C. tropicalis, 11 C. krusei, and 17 isolates from 12 other species). Resistance to fluconazole was present in 121/589 (21%) Candida species isolates in HIV-positive patients and in 2/59 (3%) in controls. Among C. albicans isolates, there were 18 fluconazole-resistant strains in HIV-positive patients (4%) and none in controls.CONCLUSIONS: Using sensitive culture methods, oral yeast colonization was detected significantly more frequently in HIV-infected patients (78%) than in a control group of HIV-negative persons (28%). In addition, yeast colonization was quantitatively more important in patients with lower CD4+ lymphocyte counts and for those who had been exposed to fluconazole for episode(s) of OPC. Fluconazole-resistant C. albicans isolates were observed only in HIV-positive patients, and all patients (17/18) for whom this information could be ascertained had had prior exposure to fluconazole.