Febrile episodes in liver transplants were prospectively evaluated. Fever was due to infections in 78% of the episodes (35 of 45) and due to noninfectious causes in 22% (10 of 45). The predominant sources of fever were bacterial infections (62%; 28 of 45) and viral infections (6%; 7 of 45), whereas rejection accounted for only 4% of the episodes (2 of 45). Forty percent of the infections were unaccompanied by fever; fungal infections were significantly less likely to be associated with fever than were viral or bacterial infections (P = .001). Eighty-six percent (6) of the 7 febrile viral infections were due to viruses other than cytomegalovirus, of which human herpesvirus-6 was the predominant pathogen (71%; 5 of 7). Eighty percent (four) of the five febrile episodes with leukopenia were due to human herpesvirus-6. Episodes of fever were most likely to occur within 12 weeks (58%) or 1 year (29%) after transplantation; 100% of the latter episodes were in patients with recurrent hepatitis due to hepatitis C virus, malignancy, or chronic hemodialysis. In conclusion, cytomegalovirus and rejection were no longer the predominant etiologies of fever in liver transplant recipients, and viruses other than cytomegalovirus (e.g., human herpesvirus-6) are emerging as a significant cause of febrile viral illnesses in these patients.