IgE-binding protein (epsilon BP) was originally identified in rat basophilic leukemia (RBL) cells by virtue of its affinity for IgE. epsilon BP is now known to be a beta-galactoside-binding lectin containing an S-type carbohydrate recognition domain. It is identical to a macrophage surface antigen, Mac-2, and lectins designated as CBP35, L-34, and RL-29, for which various functions have been suggested. Studies from other groups as well as ours have indicated that epsilon BP is secreted by cells such as macrophages and is present in extracellular fluids. We demonstrated previously that binding sites for epsilon BP are present on the surface of RBL cells. In this report, we show that epsilon BP binds to a small number of glycoprotein species on the surface of RBL cells. Significantly, one of these glycoproteins is the high-affinity IgE receptor (Fc epsilon RI). Preliminary studies showed that epsilon BP causes mediator release from RBL cells, possibly through cross-linking of Fc epsilon RI. The results suggest a function of epsilon BP as an activator of mast cells.