Sch 56592 is a new triazole derivative that possesses potent, broad-spectrum antifungal activity. We evaluated the in vitro activity of Sch 56592 compared with that of itraconazole, amphotericin B and 5-fluorocytosine against 51 clinical isolates of filamentous fungi, including Aspergillus flavus (10), A. fumigatus (12), Fusarium spp. (13), Rhizopus spp. (6), Pseudallescheria boydii (5), and one isolate each of Acremonium spp., A. niger, A. terreus, Paecilomyces spp., and Trichoderma spp. In vitro susceptibility testing was performed using the microdilution broth method outlined in the NCCLS 27-A document. Sch 56592 was highly active against A. flavus (MIC90, 0.25 micrograms/ml), A. fumigatus (MIC90, 0.12 micrograms/ml), P. boydii (MIC50, 1 microgram/ml) and Rhizopus spp (MIC50, 1 microgram/ml). By comparison with itraconazole, Sch 56592 was four-to eight-fold more active against isolates of Aspergillus and both compounds showed equipotent in vitro activity against P. boydii and Rhizopus spp. Sch 56592 was four- to 16-fold more active than amphotericin B against Aspergillus spp. and P. boydii and both antifungal drugs displayed similar activity against Rhizopus spp. Overall, Sch 56592 showed good in vitro activity against all isolates tested (MIC, < or = 2 micrograms/ml) except isolates of Fusarium (MIC range, (1-->4 micrograms/ml). On the basis of these data Sch 56592 has promising activity against Aspergillus spp. and other species of filamentous fungi that are likely to be encountered clinically. Additional in vitro and in vivo studies are warranted.