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Adenovirus infection and lymphoid hyperplasia have been associated with childhood intussusception. However, the extent of other viruses involved in this condition remains unclear. This prospective study investigates the relationship between some lymphotropic viruses and current childhood intussusception.Patients with intussusception encountered in a pediatric emergency department in a recent 3-year period were studied. Healthy infants and toddlers of comparable age served as controls. Throat and rectal viral cultures were performed in patients and controls. Viral antibodies against adenovirus, cytomegalovirus, human herpesvirus (HHV)-6, HHV-7 and Epstein-Barr virus (EBV) were tested in paired sera from the patients. Acute stage serum from each patient and mesenteric lymph nodes from patients requiring surgery were studied for the presence of adenovirus genome by PCR.Twenty-seven of 61 (44.3%) intussusception patients, but only 2 of 52 (3.8%) healthy controls shed nonenteric adenovirus in throat and rectal specimens (P < 0.001). Of the 27 (74.1%) patients who shed adenovirus, 20 were older than 1 year old, whereas only 1 of 15 (6.7%) similarly aged patients in a previous study from the same area three decades ago did so (P = 0.001). Among 43 patients with available paired sera, acute primary viral infection was found in 17 (39.5%) by adenovirus, 4 (9.3%) by HHV-6, 5 (11.6%) by HHV-7, 2 (4.7%) by EBV and none by cytomegalovirus. Multiple viral infections occurred in 6 patients. Adenovirus genome was detected in 4 of 9 mesenteric lymph nodes and in only 3 of 60 (5%) acute phase sera.Primary nonenteric adenovirus infection contributes to current childhood intussusception. Acute primary HHV-6, HHV-7 and EBV infections also play etiologic roles.