Protracted diarrhea of uncertain etiology is a significant problem following intestinal transplantation. We report an infant who developed severe secretory diarrhea 178 days after intestinal transplantation that persisted for more than 120 days. Repeated allograft biopsies demonstrated only nonspecific inflammation. Enzyme immunoassay (for rotavirus), culture, and reverse transcription polymerase chain reaction [calicivirus (Norwalk-like virus)] were used to identify the allograft viral infection. A heavy density of calicivirus RNA nucleotide sequences (genogroup II, strain Miami Beach) was isolated from the jejunal and ileal allograft. Following a reduction in immunosuppressive therapy, diarrhea and enteritis remitted in association with the disappearance of all calicivirus RNA sequences. Calicivirus may cause severe allograft dysfunction in intestinal transplant recipients.