Previous studies of infections with influenza A in animal models have stressed the tropism of this virus for the upper respiratory tract. To assess the interaction of influenza A virus with human respiratory tissue, we maintained adenoids, consisting of ciliated epithelium with underlying lymphoid follicles, in organ culture. When the organ cultures were inoculated with wild-type influenza A/Alaska (H3N2), epithelial damage and migration of inflammatory cells from the follicles into the lamina propria were seen. Growth of the virus and ciliary damage in infected organ cultures from seronegative donors were significantly greater than that seen in organ cultures from seropositive donors. Adenoidal lymphocytes were then studied to determine which factors might modulate infectivity. Specific in vitro production of antibody to influenza A/Alaska was demonstrated by adenoidal lymphocytes from seropositive donors, whereas lymphocytes from seronegative donors did not produce antibody. The human adenoid organ culture provides an attractive model to study the pathogenesis of influenza A infections and the resultant local immune response.