The National Committee for Clinical Laboratory Standards reference broth macrodilution method for antifungal susceptibility testing was compared with the E test by testing 86 clinical isolates of Candida spp. and Cryptococcus neoformans. The MIC agreement rates for the two methods for Candida spp. were 73-89% within +/-1 doubling dilution and 87-100% within +/-2 dilutions. For C. neoformans, agreement within +/-1 dilution was > 70% for all the agents tested except fluconazole for which agreement was 35%. Our data support the further evaluation of the E test as an alternative method for antifungal susceptibility testing. However, E test MICs of fluconazole for C. neoformans, particularly C. neoformans var. gattii should be interpreted with caution, as falsely elevated MICs may occur.