Staphylococcus aureus protein A-positive bacteria have recently been proposed as selective B lymphocyte mitogens. We have studied the lymphocyte response to such mitogens in bacteria in normal subjects and in patients with primary immunodeficiencies. Patients with primary T cell defects show a normal response to protein A-positive bacteria and impaired responses to PHA and Con A. In contrast, patients with Bruton agammaglobulinaemia respond normally to these T cell mitogens but not to the bacteria. Thus, protein A-positive bacteria fulfil the criteria for being a T cell-independent B cell mitogen for human peripheral blood cells.