Abstract The possibility that ingested antigens may play a role in the pathogenesis of systemic lupus erythematosus (SLE) has not been previously studied. Because this might be of considerable importance, a study was undertaken to examine the occurrence of antibodies to bovine gamma globulin (BGG) and bovine serum albumin (BSA) in SLE sera. In addition, an assay for the detection o f trace amounts o f BGG in human serum was developed. Antibodies to BGG were found in over 60 per cent of SLE sera and in 40 per cent of normal sera. Fifty per cent of normal sera and 40 per cent of SLE sera bound significant amounts of BSA. However, there was a prevalence of higher levels of antibody to both antigens in SLE. Although this may simply represent another example of hyperreactivity in SLE, both BGG and BSA are commonly ingested proteins. If antigenically intact molecules enter the circulation of certain patients, potentially pathogenic immune complexes might be formed. This possibility is supported by the finding of a BGG-like material in at least two sera, and in one case the coexistence of this material and antibodies to BGG was demonstrated. Since exposure to ingested antigens is a continual occurrence, the potential role of a wide variety of food antigens in the immune complex diseases should be carefully evaluated.