Intact (heat-inactivated) bacteria and isolated cellular components of pathogenic group A (M type 5 or 12). B. C. and G streptococci were used to evaluate the in vitro reactivity of mononuclear cells (MNC) from peripheral blood of healthy donors and from human tonsils. High doses of A-streptococcal cells, cell walls, and cell membranes stimulated DNA synthesis, production of leukocyte migration inhibitory factor (LIF), and immunoglobulin (Ig) secretion in MNC from all donors. A streptrococci stimulated higher proliferation rates and larger numbers of plaque-forming cells (PFC) in tonsil cell cultures than in blood MNC cultures. Polyclonal activation of both tonsil and blood B lymphocytes by A-streptococcal cell components was T cell and monocyte dependent, thus showing a similarity between these structures and pokeweed mitogen (PWM), which is a polyclonal T-cell activator (PTA). Cocultivation studies demonstrated that, in the presence of A streptococci, precultured MNC and T cells can suppress the blastogenic and PFC responses of autologous fresh MNC stimulated by phytomitogen or antigen, which is very similar to the concanavalin A (Con A)-induced activation of suppressor cells. In contrast, similar group B-, C-, and G-streptococcal cell envelope biostructures failed to activate blood or tonsil lymphocytes to proliferate, differentiate, or produce LIF.