Yeast strains isolated from the oropharynx of 87 consecutive patients infected with human immunodeficiency virus type 1 were examined for in vitro susceptibility to fluconazole. Candida albicans was isolated from 73 patients. Fifty-one patients had received antifungal therapy in the month preceding the yeast infection. Thirty-two patients had symptomatic oropharyngeal candidiasis. The MICs were correlated with azole use and with clinical symptoms and signs. Although there is overlap between groups, in vitro testing identified a large group of patients for whose yeast isolates the fluconazole MICs were high and who remained symptomatic while receiving azole therapy. This study supports the ability of in vitro testing to predict the clinical outcome of mucosal fungal infections. The study also demonstrates that azole resistance of oropharyngeal yeasts is a common problem in patients infected with human immunodeficiency virus type 1 and that this azole resistance has clinical relevance.