The newly described microorganism 'Simkania Z' ('Z'), an obligate intracellular, penicillin-resistant microorganism most closely related to the chlamydiae, has been associated with adult community-acquired pneumonia. The possible involvement of 'Z' in bronchiolitis in infants was examined in a prospective study of 239 infants with bronchiolitis and 78 controls. Other potential etiologic agents sought were respiratory syncytial virus (RSV), adenovirus, and cytomegalovirus. Evidence for the presence of 'Z' in nasopharyngeal wash specimens (polymerase chain reaction and/or culture) was found in 25% of infants with bronchiolitis, while controls were all negative (P < .001). A serum IgA response to 'Z' infection was detected by immunoperoxidase assay in 15% of infants with bronchiolitis versus 1.3% of controls (P < .001). Clinical findings were not different for infants with bronchiolitis associated with RSV alone, 'Z' alone, or RSV and 'Z' together. The high prevalence of 'Z' in infants with bronchiolitis, often accompanied by an immune response, suggests a possible etiologic role of this agent in the disease.