Candida guilliermondii is rarely isolated from humans. We describe a case of disseminated C. guilliermondii with associated purulent pericarditis, despite high-dose amphotericin B (AmB), in a 19-year-old female with aplastic anemia who underwent BMT. In vitro susceptibility studies of the 13 clinical isolates, two control strains and one environmental isolate revealed a minimum inhibitory concentration (MIC) range of (0.19-1.56 micrograms/ml) for AmB and (1.25-10 micrograms/ml) for fluconazole. Pulsed-field gradient gel electrophoresis was performed to evaluate possible similarities between strains. This case is significant for several reasons, the high degree and prolonged duration of fungemia despite high-dose AmB and concomitant flucytosine, the change in in vitro susceptibility during therapy, the initial misidentification of the yeast isolate, and the invasiveness of the organism. The poor response to therapy may have been due to the severe and sustained neutropenia and the high MICs of C. guilliermondii to AmB.