We investigated the correlation between in vitro susceptibility to fluconazole and clinical response in severely ill patients with oropharyngeal candidiasis treated with fluconazole. The study included 48 adult patients, of whom 23 were neutropenic (absolute neutrophil count, < 500/mm3). Forty-eight isolates (20 Candida albicans, 12 Candida krusei, 10 Candida kefyr, 3 Torulopsis glabrata, and 3 Candida tropicalis) were tested for susceptibility to fluconazole with use of the macrodilution method of the National Committee for Clinical Laboratory Standards. A strain was considered to be susceptible to fluconazole if the MIC was < or = 8 micrograms/mL and resistant if the value was > or = 64 micrograms/mL. All but one of the resistant strains were C. krusei isolates. Species of causative Candida, persistent neutropenia, and susceptibility to fluconazole were significant predictors of clinical response by univariate analysis. Logistic regression analysis indicated that the only significant factor was the species of Candida isolates, validating the recently recommended MIC breakpoint and the correlation between clinical outcome and in vitro antifungal susceptibility.