Langerhans cell histiocytosis (LCH) is an enigmatic histiocytic proliferative disorder of unknown etiology that affects children primarily. We have investigated the possibility that viruses are etiological or that they have a "triggering effect" in LCH. Sensitive in situ hybridization and polymerase chain reaction (PCR) techniques were used in 56 cases of LCH. We sought and failed to find evidence of genomes for adenovirus, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human herpesvirus type 6, human immunodeficiency virus, human T-cell leukemia virus types I and II, and parvovirus. Although some probes hybridized to tissues from several cases, PCR failed to confirm the presence of viral genome in any. We conclude that there is no evidence that these viruses are associated with LCH.