Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 g/ml) and 14 (3.6%) were resistant (MICs, >64 g/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 g/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n ؍ 250) for which MICs were <1 g/ml were compared with isolates (n ؍ 30) for which MICs were >1 g/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 g/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.Candida vaginitis remains a common problem in immunocompetent, healthy women and is predominantly caused by strains of Candida albicans (Ͼ90%) (14,17,19). Only a minority of cases (Ͻ10%) are caused by non-C. albicans Candida species, usually C. glabrata, and despite considerable debate, there is little evidence of a significant increase in infection rates due to the non-C. albicans Candida species (14,17,19). Given the reports of refractory oral and esophageal candidiasis caused by fluconazole-resistant C. albicans strains and, less commonly, non-C. albicans Candida species, it is important to monitor the fluconazole susceptibilities of vaginal isolates of the various Candida species (1,3,5,8,11). Recently, a nationwide, multicenter prospective study was performed in which the clinical and mycological efficacies of two dosage regimens of fluconazole in women with complicated Candida vaginitis were compared (19). Analysis of the in vitro fluconazole susceptibilities of these vaginal isolates forms the basis of this report. The susceptibilities of a large number of pathogenic isolates of C. albicans and non-C. albicans Candida species were determined. These determinations allowed (i) detection of preexisting and newly acquired fluconazole resistance and (ii) establishment of a correlation between in vitro susceptibility and clinica...