Lymphoid dendritic cells play an essential role in antigen presentation in primary immune responses and are believed to be important in normal healthy responses of the mucosal immune system. The microanatomical distribution of HLA-DR-positive/S100 antigen-positive dendritic cells was analyzed in 10 normal palatine tonsils. Tonsil biopsies were obtained from 8 normal children undergoing otolaryngological surgery for reasons completely unrelated to tonsil disease. Two samples of normal adult tonsil were also obtained. Standard immunohistochemical methods, with antigen retrieval, were used to detect cell surface markers in formalin-fixed and/or frozen tissue specimens. The clinical identification of these tonsils as normal was confirmed by their microscopic appearance. HLA-DR antigen expression was restricted to lymphocytes, macrophages and dendritic cells; all normal epithelia were negative. S100-positive dendritic cells were readily detected in surface and crypt epithelium and were rare in submucosal sites or follicles. T cells were observed as frequently as dendritic cells in epithelial sites. Dendritic cell density was highest in extrafollicular T cell areas, where CD4-positive lymphocytes were especially abundant. A significant correlation was observed between the total number of different bacterial species isolated from individual normal tonsils and the frequency of dendritic cells in both the crypt epithelium and extrafollicular T cell areas. The number of dendritic cells at the tonsil surface was not similarly related to the bacterial flora.