The major goal of this investigation is to determine the relationship between the natural binding of bacteria to lymphocytes and lymphocyte function. Bacteria that bind naturally to human lymphocytes have been found or obtained by mutation and selection. The lymphocyte subpopulations have been subdivided based on this binding into B and T cells and two B (B1 and B2) and four T-cell subpopulations (T1 to T4). The relationship between the cells identified by bacteria and by the commercially available monoclonal antibodies using two-color fluorescence has been investigated. The T-cell subpopulations have been separatedby adherence to bacterial monolayers. It has been found that the Ia+ cells from normal human blood also bound B. melitensis but Ia is not the structure involved in this binding. T1T2 cells contained all the precursors for the cytotoxic cells developed in mixed lymphocyte reaction,but they contained only a fraction of the OKT-8+ cells. The contact of cells with bacteria appeared to have an adjuvant effect on the development of these cytotoxic cells. The T3T4 cells are only slightly better than T1T2 cells in helping B cells secrete Ig in cultures stim-ulated by pokeweed mitogen (PWM). Since T4 cells contained all the natural killer (NK), do not bind any bacteria, and it appears that bacteria bind to lectins on lymphocytes, the possibility is being investigated that the targets of NK cells are abnormal for differentiation lectins. Bacteria are now being selected to bind to these lectins. The hypothesis that malignant lymphoid cells express lectins and these lectins are important to the control of their proliferation was tested in a clinical condition. It has been found that in patients with chronic lymphocytic leukemia, the binding index for bacteria is a good prognostic indicator. We suggested that the loss of lectins is an escape mechanism that allows the cells to proliferate out of control. (2)