Stimulation with glucocorticoids of mouse splenic lymphocytes and peritoneal adherent cells resulted in the formation of a soluble factor--i.e., glycosylation inhibiting factor (GIF)--that inhibits the assembly of N-linked oligosaccharide(s) to IgE-binding factors during their biosynthesis. The major cell sources of GIF are Lyt 2+ I-J+ T cells and macrophages, respectively. The molecular size of GIF from T cells was 15 kDa, while GIF from macrophages consisted of 40- and 15-kDa molecules. GIF from both cell sources bound to monoclonal antibody against lipomodulin and exerted phospholipase inhibitory activity upon dephosphorylation. In view of previous reports that glucocorticoids induce the formation of phospholipase inhibitory protein--i.e., lipomodulin/macrocortin--GIF from T cells and macrophages appear to be phosphorylated derivatives of lipomodulin. GIF released from splenic lymphocytes and macrophages of C57BL/6 mice bound to anti-I-Jb antibodies but not to either anti-I-Jk or anti-I-Js antibodies. Upon stimulation with glucocorticoids, CBA and B10.A(5R) lymphocytes released GIF that bound to anti-I-Jk antibodies but not to anti-I-Jb antibodies, while the same factor from B10.A(3R) lymphocytes bound to anti-I-Jb antibodies. The results indicate that I-J determinants are associated with lipomodulin/macrocortin from T cells and macrophages.