Candida rugosa was isolated from two patients. One patient had acute leukemia and developed invasive disease due to this yeast on two occasions while granulocytopenic. Her infection was eventually cured after treatment with amphotericin B. In another immunocompromised patient, the yeast was isolated from the sputum in the presence of a pulmonary infiltrate, but there was no other evidence for a pathogenic role. Antifungal susceptibility testing of the first patient's isolate and three environmental isolates showed all four to be susceptible to amphotericin B, miconazole, and flucytosine, and only the patient isolate was resistant to ketoconazole. These results suggest possibilities for therapy in future encounters. It appears that C. rugosa, a common pathogen in cattle, can be pathogenic in humans under the appropriate circumstances.