The goal of this study was to determine the influence of bacterial translocation on systemic immunity, since bacteria and their products play a major role in the development and maintenance of the host's immune system. To test this hypothesis, we measured the blastogenic response of mononuclear cells harvested from the blood, spleen, Peyer's patches, and mesenteric lymph nodes of control and Escherichia coli C25 monoassociated mice to a battery of mitogens. The E. coli C25 monoassociation model was used because this bacterial translocation model is not associated with experimental manipulations that are likely to affect the systemic immune system. The mitogenic response of lymphocytes isolated from the E. coli C25 monoassociated mice was significantly depressed compared to the control groups (p less than 0.01). Since the biologic significance of depressed in vitro mitogen responsiveness is difficult to determine, we assessed the ability of the mice to control a bacterial challenge using an in vivo Staphylococcus aureus abscess model. It appears that the observed changes in mitogen responsiveness may be of biologic significance, since the ability of the E. coli C25 monoassociated mice to control the injected S. aureus was impaired (p less than 0.01). These results suggest that an association exists between bacterial translocation and decreased systemic immune responsiveness.