A point prevalence study to document oral yeast carriage was undertaken. Risk factors for the development of oropharyngeal colonization or infection by fluconazole-resistant Candida strains in HIV-infected patients were investigated with a case-control design. Cases included all patients with fluconazole-resistant strains (MIC> or =64 microg/ml), and controls were those with susceptible (MIC< or =8 microg/ml) or susceptible-dependent-upon-dose (MIC 16-32 microg/ml) strains. One hundred sixty-eight Candida strains were isolated from 153 (88%) patients, 28 (16%) of whom had oropharyngeal candidiasis. Overall, 19 (12%) of the patients harbored at least one resistant organism (MIC > or = 64 microg/ml). Among patients with resistant strains, tuberculosis (P<0.001), esophageal candidiasis (P = 0.001), clinical thrush (P<0.001), and a CD4 + cell count < 200/mm3 (P = 0.03) were more frequent. These patients had also been treated more commonly with antituberculous drugs (adjusted odds ratio [OR] 6.13; 95% confidence interval [CI] 2.11-17.80), ciprofloxacin (OR 6.0; 95% CI 1.23-29.26), fluconazole (OR 4.59; 95% CI 1.55-13.52), and steroids (OR 4.13; 95% CI 1.11-15.39). Multivariate analysis showed that the determinants for fluconazole resistance were therapy with antituberculous drugs (OR 3.61; 95% CI 1.08-12.07; P=0.03) and one of the following: previous tuberculosis (OR 3.53; 95% CI 1.08-14.57; P=0.03) or fluconazole exposure (OR 3.41; 95% CI 1.10-10.54). Findings from this study indicate that treatment with antituberculous drugs, previous tuberculosis, and fluconazole exposure are the strongest determinants for development of oropharyngeal colonization or infection by fluconazole-resistant Candida strains in HIV-infected patients.