We determined the in vitro susceptibilities of 643 strains of Candida spp., representing 13 species rarely isolated from blood, to ravuconazole as well as three licensed systemic antifungal agents (amphotericin B, fluconazole, and flucytosine). The organisms included 234 isolates of C. krusei, 102 isolates of C. guilliermondii, 103 isolates of C. lusitaniae, 18 isolates of C. famata, 29 isolates of C. kefyr, 20 isolates of C. pelliculosa, 13 isolates of C. rugosa, 101 isolates of C. dubliniensis, 4 isolates of C. inconspicua, 11 isolates of C. lipolytica, 1 isolate of C. sake, and 2 isolates of C. lambica and 5 isolates of C. zeylanoides. MIC determinations were made by the National Committee for Clinical Laboratory Standards reference broth microdilution method and Etest (amphotericin B). Ravuconazole demonstrated excellent activity (98% susceptible at MIC < or = 1 microg/mL) against all species with the exception of C. inconspicua (75% [3 of 4]). By comparison, decreased susceptibility to fluconazole and/or amphotericin B was observed among isolates of C. krusei, C. guilliermondii, C. famata, C. rugosa, C. inconspicua, and C. lambica. These findings illustrate the fact that many of the less common species of Candida exhibit decreased susceptibility to one or more of the established systemically active antifungal agents. Ravuconazole is clearly an "extended-spectrum" triazole with potent in vitro activity against these rare and potentially "emerging" opportunistic pathogens.