Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomaviruses (HPVs). It is characterized by multiple recurrences of benign neoplasms and has a variable clinical course, ranging from infrequent recurrence to acute airway obstruction. One way in which HPV subverts the immune system in RRP is by interfering with TAP1 (transporter associated with antigen presentation 1). We examined whether a known TAP1 polymorphism in the ATPase domain altered the severity of disease in patients with RRP. The presence of this polymorphism was significantly correlated with severity of disease (P=.015). Because of the proximity of the TAP1 gene to human leukocyte antigen (HLA) class II genes on chromosome 6, we postulated that a linkage disequilibrium may exist. Of the patients with polymorphic TAP1, 36% were positive for HLA-DRB1*0102 (P=.021; P=.147 with Bonferroni's correction). However, this association appeared to mitigate the severity of disease (P=.04). Therefore, severity of disease in a patient with RRP might be determined by sequencing TAP1, in conjunction with HLA class II genes.