We have compared the activities of posaconazole and other currently available antifungal agents against a collection of 3,378 clinical isolates of yeasts and filamentous fungi. A total of 1,997 clinical isolates of Candida spp., 359 of other yeast species, 697 strains of Aspergillus spp., and 325 nondermatophyte non-Aspergillus spp. were included. The average geometric means of the MICs of agents that were tested against Candida spp. were 0.23 g/ml for amphotericin B, 0.29 g/ml for flucytosine, 0.97 g/ml for fluconazole, 0.07 g/ml for itraconazole, 0.04 g/ml for voriconazole, 0.15 g/ml for caspofungin, and 0.03 g/ml for posaconazole. Voriconazole and posaconazole were active in vitro against the majority of isolates, with resistance to fluconazole and itraconazole, and against Cryptococcus neoformans and other Basidiomycota yeasts. Posaconazole was the most active of antifungal agents tested against Aspergillus spp., with an average geometric mean of 0.10 g/ml. It was active against Paecilomyces spp., Penicillium spp., Scedosporium apiospermum, and some black fungi, such as Alternaria spp. Multiresistant filamentous fungi, such as Scedosporium prolificans, Scopulariopsis brevicaulis, and Fusarium solani, were also resistant to voriconazole, caspofungin, and posaconazole. Amphotericin B and posaconazole were found to be active against most of the Mucorales strains tested. Posaconazole and currently available antifungal agents exhibit a potent activity in vitro against the majority of pathogenic fungal species.Posaconazole is a new triazole agent with an extended spectrum of in vitro activity. It is active against opportunistic, endemic, and dermatophytic fungi (10, 13, 14, 15) as well as Candida, Cryptococcus, and other yeast species (1,3,17,22,23), including isolates that exhibit resistance to fluconazole and itraconazole (3,10,23). It also has a potent activity in vitro against Aspergillus species; posaconazole appears to be more active in vitro against Aspergillus than are amphotericin B, itraconazole, voriconazole, and ravuconazole, inhibiting 95% of isolates at a MIC of Յ1 g/ml (2, 9, 24). In addition, the new triazoles have been shown to have antifungal activity against other species of filamentous fungi, such as Penicillium spp., Paecilomyces spp., and Acremonium spp., and Sporothrix schenckii as well as some isolates of Fusarium spp., Scedosporium apiospermum, and black fungi (9,10,13,18,24,30). Most notably, posaconazole is more active than the other triazole compounds against zygomycetes, with MICs around or below 1 g/ml. Within the class of Zygomycetes, posaconazole appears to be more active against Rhizopus spp. and Absidia corymbifera than against Mucor spp., which is consistent with the prior observation that the zygomycetes appear to be a heterogeneous group with regard to their susceptibilities to antifungal agents (7,9, 16,24,29).We have analyzed the in vitro activity of posaconazole and other currently available antifungal agents against a collection of 3,378 clinical isolates of yeasts and fila...