The antibody response to immunization with Brucella and the levels of natural antibody to Escherichia coli and Shigella were compared in patients with systemic lupus erythematosus and control groups. After Brucella immunization, SLE patients showed a significantly lower antibody response in whole serum and in the macroglobulin antibody fraction separated by sucrose density gradient centrifugation. Sucrose gradient fractionation of natural antibodies to E. coli and a polyvalent Shigella antigen showed a significant decrease in macroglobulin antibody against four of the five E. coli antigens tested and the Shigella polyvalent antigen in SLE patients when compared with a group of normal individuals and a matched control group with pulmonary tuberculosis. Whole serum natural antibody titers against 5 of 13 Shigella antigens were significantly lower in the SLE patients when compared with the normal group, and against 7 of 13 when compared with the matched tuberculosis controls. Whole serum titers against 8 of 13 E. coli antigens were significantly lower in the SLE patients when compared with normal subjects. The observed decreased antibody response to bacterial antigens in SLE patients, occurring mainly in the macroglobulin fraction, is discussed in relation to the increased incidence of infection commonly observed in these patients.