Five antigenically distinct serotypes of human papillomavirus (HPV) cause various cutaneous verrucae with distinct clinical features. Laryngeal and other mucosal papillomas, also suspected to have a viral etiology, were examined for the presence of a genus-specific (common) antigen of HPV using a peroxidase-antiperoxidase (PAP) technique. The primary antiserum used was reactive against laryngeal papillomas from 26 of 35 randomly selected patients (74%); overall, 49 of the 102 squamous papillomas stained were positive for HPV (48%). HPV antigen was not demonstrated within frankly dysplastíc squamous cells. Nuclear localization of virus was confirmed by electron microscopy in 3 cases positive for HPV. PAP localization of HPV is rapid and more efficient than routine electron microscopy. Our data indicate a common pathogenesis for some papillomas and cutaneous verrucae and suggest a future role for immunohistochemistry in evaluating the epidemiology and pathobiology of laryngeal papillomatosis.