In a haemolytic plaque assay staphylococcal strain Cowan 1 was shown to induce polyclonal antibody secretion in human blood lymphocytes, whereas Haemophilus influenzae and Escherichia coli gave low responses. Diplococcus pneumoniae and haemolytic streptococci generally did not activate blood cells. All five bacteria could activate spleen, tonsil and adenoid cells both to polyclonal Ig secretion and increased DNA synthesis. Thus blood cell reactivity does not necessarily reflect the response pattern in other lymphatic organs. The adenoid was shown to contain lymphocytes more responsive to bacteria normally residing in nasopharynx than cells residing in other lymphatic organs. On the other hand, spleen and mesenteric lymph node contain a subpopulation of cells highly responsive to bacteria such as Escherichia coli normally residing in the bowel. Therefore, we conclude that there exists a functional compartmentalization of lymphocytes in distinct secondary lymphoid organs.