The ability of bovine IgG preparations to bind to the various distinct human leukocyte Fcγ receptors was studied. In experiments using intact cells and isolated Fcγ receptors, it was demonstrated that bovine IgG can bind to Fcγ receptors of four human cell types but not to Fcγ receptors of human neutrophils. 125I-labeled Fcγ receptors purified on human IgG-Sepharose columns from human B and T lymphocytes, monocytes and eosinophils were able to rebind specifically to insolubilized bovine IgG. In contrast, radioiodinated human neutrophil Fcγ receptors did not rebind to bovine IgG-Sepharose. A similar pattern of specificity was demonstrated in studies of the binding of 125I-labeled heat-aggregated bovine IgG to various human leukocyte populations. The labeled aggregated bovine IgG bound to peripheral blood mononuclear cells, to B cells from chronic lymphocytic leukemia patients and to macrophage-like U-937 cells, but bound poorly to normal human granulocytes. Labeled non-aggregated bovine IgG was not appreciably bound to any of the cell populations. Since bovine IgG in dietary sources is frequently exposed to heat, the effect of heating on the physical state and Fc-binding properties of bovine IgG was examined. The data show that heating bovine IgG at concns of 0.9-3.6 mg/ml at 63°C for 30 min in neutral buffer causes aggregation of bovine immunoglobulin (10-16% aggregation) and increases the ability of bovine IgG preparations to bind to human Fcγ receptors of intact cells. Gel filtration studies suggest the possibility that bovine IgG may also be aggregated during the pasteurization of raw milk.