A new inhibitor of IgE-mediated allergic reactions has been studied in rats. This new inhibitor is chemically different from cromoglycate and shows qualitative and quantitative advantages over it. It is 2,500 times more active in rats than disodium cromoglycate and shows oral activity. This new inhibitor possesses no bronchodilator or end-organ antagonism activity and does not raise intracellular cAMP levels but as cromoglycate acts by inhibition of mediator release. Multiple high (25 mg/kg) doses in rats lead to tachyphylaxis. This effect is reversed both by decreasing the first dose and increasing the time between doses. Over a 5- to 10-fold concentration range, this inhibitor in mast cells can be stimulatory or inhibitory to ⁴⁵Ca⁺⁺ flux into cells. This ability to inhibit ionophore-induced ⁴⁵Ca⁺⁺ flux correlates well with inhibition of histamine release.