OBJECTIVES: A pilot study was designed fo analyze lymphoid cell infiltration in Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinomas (NPCs) and to determine whether this pattern of infiltration is consistent' with non-EBV+ head and neck carcinomas or with solid EBV+ tumors in other locations. STUDY DESIGN: We performed a retrospective analysis of archived NPCs and oral cavity carcinomas. METHODS: Immunohistochemical staining of the archive material for various markers (CD3, CD8, UCHL-1, S-100, and intercellular adhesion molecule) was performed. Polymerase chain reaction techniques to establish the presence of the EBV genome were used. Cells in different locations were counted under a light microscope by 2 of the authors. RESULTS: The infiltration pattern of HPCs was different from that of oral cavity carcinomas. Stromal infiltration was significantly denser in oral cavity carcinomas. Tumor nest infiltratlon was more pronounced in NPCs. The pattern of infiltration was comparable with what has been described for other solid EBV+ tumors. CONCLUSIONS: The immune response to NPCs is likely to be strongly influenced by the presence of the EBV genome. The pattern of infiltration is similar to that of other non-head and neck EBV+ solid tumors and different from that of EBV- head and neck carcinomas.