The sites of interaction between antigen-presenting cells (dendritic cells, macrophages) and lymphocytes in the human palatine tonsil were investigated by pre-embedding immuno-electron microscopy and acid-phosphatase histochemistry. Used in this study were: an S-100 protein antiserum recognizing Langerhans cells and interdigitating cells, OKT6 monoclonal antibody reacting with surface antigens of Langerhans cells, and Leu-3a monoclonal antibody directed to surface antigens of helper-T-cells. In the stratified squamous epithelium, Langerhans cells with characteristic rod-shaped or racket-shaped Birbeck granules exhibited S-100 protein and OKT6 immunoreactivites, and frequently extended long processes to adjacent lymphocytes. The subepithelial area contained a significant number of macrophages, some of which were closely apposed to interdigitating cells with S-100 protein immunoreactivity. Occasionally, macrophages with acid-phosphatase-positive phagosomes and/or lysosomes extended short processes to neighboring lymphocytes. In the interfollicular area, some interdigitating cells and a few Langerhans cells were seen in proximity to or in contact with lymphocytes stained with the Leu-3a antibody. These findings support previous in vitro studies suggesting the induction of T-cell activation by antigen-presenting cells. They further indicate that T-cell activation by the individual antigen-presenting cells takes place in different areas of the human palatine tonsil through a variety of cell-to-cell interactions.