Isolation of fluconazole-resistant strains of Candida species from human immunodeficiency virus (HIV)-infected patients after repeated or continuous courses of treatment has been reported with increasing frequency. During 1991-1992, MICs of fluconazole for 139 Candida albicans isolates from our institution were bimodally distributed: 102 strains were susceptible (MICs, < or = 4 micrograms/mL) and 37 were resistant (MICs, > or = 8 micrograms/mL). There was incomplete cross-resistance between fluconazole and ketoconazole or miconazole, and there was no cross-resistance between azoles and amphotericin B or flucytosine. Twenty of the 37 fluconazole-resistant strains were isolated from 17 HIV-negative patients, some with systemic infections, who had never been treated with azoles. There were no differences in characteristics or risk factors for those patients as compared with those for an equal number of HIV-negative patients from whom fluconazole-susceptible strains were isolated. Among patients with systemic infection, 6 (50%) of 12 with infection caused by fluconazole-resistant strains survived and 11 (69%) of 16 with infection caused by fluconazole-susceptible strains survived (P = .54). Survival was not found to be related to treatment regimen, but the number of patients was small. The emergence of fluconazole-resistant C. albicans among HIV-negative patients never exposed to azoles is of concern.