Oral inoculation of infants with a vaccine that contains simian-human reassortant rotaviruses has been found to be a rare cause of intussusception. Because intussusception can be associated with enlargement of gut-associated lymphoid tissue, we studied the capacity of simian-human and bovine-human reassortant rotaviruses to cause lymphoid hypertrophy and hyperplasia of Peyer's patches (PP) of adult BALB/c mice. Neither hypertrophy nor hyperplasia was detected in PP after oral inoculation with simian-human or bovine-human reassortant rotaviruses. However, infectious virus was detected in PP and mesenteric lymph nodes after oral inoculation with simian, but not bovine, reassortant rotaviruses. Implications of these findings on the pathogenesis of intussusception are discussed.A vaccine that contains simian-human reassortant rotaviruses was found to be a rare cause of intussusception in infants [1]. The vaccine (Rotashield; Wyeth-Lederle Laboratories) contained simian rotavirus strain RRV and 3 simian-human reassortant rotaviruses. In contrast, natural infection with rotavirus is not clearly a cause of intussusception [2].Although why the simian-based rotavirus vaccine caused intussusception remains unclear, several hypotheses have been advanced. First, lymphoid enlargement in gut-associated lymphoid tissue (GALT) caused by simian rotaviruses may serve as a "lead point" for intussusception. Second, the vaccine strain may replicate in a site different from that of natural infection. Finally, the vaccine strain(s) may be processed or presented by antigen-presenting cells in a site or manner different from that which occurs after natural infection.We examined the capacity of the simian-based reassortant rotavirus vaccine to cause lymphoid hypertrophy or hyperplasia of Peyer's patches (PP) after oral inoculation of adult BALB/ c mice. In addition, we determined whether infectious rotavirus could be detected in GALT. These findings were compared with those for mice orally inoculated with either a bovine-based reassortant rotavirus vaccine or media alone.