Rat immunoglobulin E (IgE) was treated with a crosslinking reagent, dimethyl suberimidate, and fractionated by gel filtration into monomers, dimers, trimers, and higher polymers. The fractions retained substantial ability to bind specifically to mast cells. About one-third of the cell-bound dimers appeared to bind bivalently. The fractions were assayed in vivo by passive cutaneous anaphylaxis in rats, and for histamine or serotonin release in vitro using normal or tumor mouse mast cells. The monomers showed no activity, while the dimers and higher polymers gave excellent and approximately equivalent responses. We conclude that IgE that has been crosslinked to form dimers prior to the addition to mast cells can serve as a unit signal for triggering IgE-mediated exocytosis.