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The human caliciviruses, which include Norwalk-like viruses (or Noroviruses) and Sapporo viruses, commonly cause epidemic and endemic viral gastroenteritis of short duration in healthy individuals. However, the impact of human calicivirus in immunosuppressed populations has not been established. The authors report five pediatric patients who developed human calicivirus enteritis after intestinal transplantation.Infection was documented with repetitive reverse transcription polymerase chain reaction testing with nucleotide sequencing of tissue and lumen fluid specimens.A single strain, type Miami Beach, affected all patients in the hospital with an apparent index case. A potential mode of transmission was not defined. Severe osmotic or secretory diarrhea necessitated intravenous fluid therapy for 40 days or more in three of the five infants. Concurrent or recent subclinical allograft infection with adenovirus in two patients was associated with more severe symptoms. Virus excretion exceeded 80 days in two patients. Differentiation of human calicivirus enteritis from allograft rejection was difficult, as both disorders were associated with increased enterocyte apoptosis and inflammation. Intensification of immunosuppressive therapy because of suspected rejection appeared to prolong symptoms.These findings demonstrate that human calicivirus can be a significant pathogen in intestinal transplant recipients and potentially in other immunocompromised patients.