The in vitro activities of eight antifungal agents were determined against clinical (n = 63 genotype A, n = 3 genotype B) and environmental (n = 2 genotype A, n = 13 genotype B) strains of Exophiala dermatitidis. The resulting MIC(90)s for all strains (N = 81) were, in increasing order, as follows: posaconazole, 0.125 μg/ml; itraconazole, 0.25 μg/ml; voriconazole, 0.5 μg/ml; amphotericin B, 0.5 μg/ml; isavuconazole, 1 μ/ml; caspofungin, 8 μg/ml; anidulafungin, 8 μg/ml and fluconazole, 16 μg/ml. There were no significant differences in the patterns of susceptibility between genotypes A and B, environmental and clinical strains, isolates recovered from cutaneous and deep locations and strains from different geographical areas (P > 0.05). The difference in the MIC(90)s between each of these groups was not more than one dilution. The present study demonstrated that, based on in vitro activity, posaconazole and itraconazole have the highest activity against this fungus. In addition, voriconazole and the experimental broad-spectrum antifungal triazole, isavuconazole, both of which are available as intravenous preparations, have adequate activity against E. dermatitidis. However, in vivo efficacy remains to be determined.