To investigate the occurrence of lymphoid progenitor cells in human tonsils, we studied tonsils from children and adults by immunohistochemistry by using a panel of antibodies to antigens associated with lymphoid progenitor cells, including terminal deoxynucleotidyl transferase (TdT), CDl0 (CALLA), CD34, CD99 (p30/32mic2), and CD 117 (c-kit), and compared them to reactive lymph nodes. Lymphoid progenitor cells, positive for TdT, CD 10, and CD99, but not CD34 or CD1 17, were readily identified in tonsils from children and adults (TdT, 14 of 15; CD10, 15 of 15; CD99, 11 of 15), but were rarely present in lymph nodes (TdT, 1 of 8; CD 10, 1 of 8; CD99, 0 of 8). Lymphoid progenitor cells in tonsils were localized to discrete foci at the periphery of lymphoid lobules adjacent to fibrous septae. Lymphoid progenitor cells are present in human tonsils, and the tonsils are a potential site of postnatal lymphopoiesis. The presence of lymphoid progenitor cells in human tonsils should not be confused with lymphoblastic lymphoma or leukemia.