Cunninghamella bertholletiae is a saprophytic fungus found in soil. Infection with this organism is extremely rare, occurring almost exclusively in immunosuppressed hosts. There have been only three previous cases of infection with this fungus reported in solid-organ recipients. We report an unusual case of disseminated Cunninghamella infection in a woman who had received a renal transplant. A 48-year-old woman received a living-related kidney transplant for focal segmental glomerulonephritis. She was treated with plasmapheresis and muromonab-CD3 (OKT3) for two episodes of rejection. Because of recurrent focal segmental glomerulonephritis with diuretic-resistant edema, she underwent transplant nephrectomy, was restarted on hemodialysis, and had her immunosuppression stopped. Shortly thereafter, the patient presented with pulmonary infiltrates and hemorrhagic stroke with a rapidly fatal course. Autopsy revealed widely disseminated C bertholletiae involving the central nervous system, lungs, and heart. This is the first reported case of endocarditis caused by this organism. Diagnosis of this fungal infection is often difficult. Because the few patients who have survived this infection seemed to have been diagnosed early, it is important for clinicians caring for transplant patients to be aware of this invasive infection. Successful treatment requires prompt diagnosis and high-dose amphotericin B.