We examined human papillomavirus (HPV) infection in biopsy specimens and cellular scrapes that were taken from respiratory papillomas and six nondiseased sites from the respiratory tract of seven patients. Human papillomavirus was detected by polymerase chain reaction amplification, followed by DNA hybridization with probes for specific HPV types. All papillomas (100.0%, n = 5) were positive only for HPV type 6 or 11. In the nondiseased site specimens, 61.3% (19/31) of the specimens were positive, again only for HPV type 6 or 11. Among the nondiseased site specimens from the cervical trachea, intrathoracic trachea, and bronchus, 80% to 100% were HPV positive compared with only 25% to 50% of HPV infection detected in the nasopharynx, posterior tonsillar pillar, and aryepiglottic fold. These results support the tenet that HPV infection is present in clinically normal respiratory tract tissue and that the reservoir site of reinfection is more commonly in the lower airway. However, patients with upper-airway involvement were more likely to be diagnosed as having severe disease.