Seventy-two children with chronic inflammatory bowel disease were investigated for infections with various viruses and Mycoplasma pneumoniae, Chlamydia psittaci, and Coxiella burnetii to determine whether these pathogens are associated with acute onset exacerbations. Altogether 54 infections were identified serologically, of which 23 (42.6%) were associated with exacerbations. This corresponded to 24.2% of the recorded exacerbations during the study period. The respiratory pathogens accounted for 59.3% of the infections and 43.8% of these were associated with gastrointestinal symptoms. This is consistent with the observation that up to 40% of the exacerbations were associated with symptoms of antecedent or concurrent infection, most commonly involving the respiratory tract. Rubella virus, Epstein-Barr virus, and adenovirus were associated with acute exacerbations in 5 children. Thus, common pathogens were frequently associated with exacerbations and account for a large proportion of the commonly reported symptoms of a concurrent infection. The possible causal relationship between these pathogens and exacerbation of inflammatory bowel disease is discussed. Reactivation of latent herpesviruses was identified in 4 children with active disease and indicates that the converse relationship may also occur.