Understanding the immunological structure of the upper aerodigestive tract is important for analysing the interaction between incident challenges, such as human papillomavirus infection, and disease, particularly head and neck cancer. We have shown previously that tonsillar and laryngeal epithelium express major histocompatibility complex (MHC) class II locus products, but that expression of human leucocyte antigen (HLA)-DQ is reduced compared to HLA-DR. This may confer a decreased repertoire of presented T cell epitopes generated by the processing of exogenous peptides in upper airway mucosa. To determine whether the peptide repertoire presented by MHC class I loci varies in stratified squamous epithelium, laryngeal and tonsillar biopsies were taken from 19 otherwise healthy patients (M : F 6 : 13, 16-64 years). Quantitative immunofluorescence microscopy, using antibodies to MHC class I alpha-chain (pan-locus specific, HLA-A, HLA-B + C) and beta(2)-microglobulin, showed lower expression of the alpha-chain in laryngeal and tonsillar epithelium than in either lamina propria (tonsil 73% versus 89%, P < 0.0001; larynx 68% versus 85%, P < 0.005). Within the epithelium itself, the intensity of alpha-chain expression decreased from the basal to apical layers. In paired squamous epithelia from the two sites, alpha-chain expression was significantly higher in the tonsil compared to the larynx (79% versus 62%, P < 0.05). We suggest that these findings reflect functional stratification of these epithelia with the superficial layer, most exposed to incident challenges, less equipped to present antigens to conventional T cells. This may affect immunosurveillance directed at viral and tumour-related epitopes in the upper airway.