Hepatosplenic candidiasis (HSC) is a morbid complication encountered in immunocompromised individuals, especially, those being treated with intensive chemotherapy protocols for acute leukemia. Immediate recognition of this complication and initiation of appropriate treatment is crucial in order to control the infection, decrease the morbidity and mortality, and avoid delays in treatment of the underlying condition. The definitive diagnosis requires either positive blood cultures for yeasts in the presence of abnormal findings on imaging studies consistent with HSC, or liver biopsy demonstrating yeast forms or pseudohyphae. We describe our experience in the evaluation of 15 patients with HSC using magnetic resonance imaging (MRI) as a diagnostic and follow-up tool. The diagnosis of HSC was established by liver biopsy in 11 patients (73%), and by positive blood cultures for Candida in 4 patients (27%). All patients had MRI findings consistent with HSC during the study period. Amphotericin B was administered intravenously to all 15 patients (median duration of treatment, 62 days). Repeat MR images were obtained at 2 weeks, 6 weeks and then at monthly intervals until the resolution of abnormalities. The median time for the disappearance of MRI lesions was 9 weeks. Alterations in the appearance of lesions on MRI were noted throughout chemotherapy in all the 13 (86.6%) responding patients. Our results suggest that MRI when used in patients with high clinical suspicion for HSC provide an alternative for liver biopsy or other invasive diagnostic procedures and that appropriate response to treatment can be safely monitored by obtaining sequential MRI studies.