Recent evidence and speculation regarding the dynamic structure of biological membranes is combined with information on the pharmacology and biochemistry of the allergic histamine release reaction to formulate a model which can explain many of the observed events in this reaction, and especially tie presumed early enzymological events to pharmacologically controlled subsequent events. It is proposed that the reaction of the cell-bound antibodies with suitable antigens causes a membrane deformation or a displacement of hydrophilic residues within the membrane in such a manner that there is a local clustering or polarization of charges. Biochemically, the earliest event may be the activation of a membrane-bound chymotrypsin-like proesterase. A speculative step in the proposed sequence is the activation of a membrane-bound pro-phospholipase A by the activated esterase. The local, limited action of the phospholipase A on the membrane lipids could influence the action of membrane-bound ATPase and nucleotide cyclases in several ways. The resulting local decrease in the concentration of cyclic AMP, is a condition which is known to modulate antigen-induced histamine release. It is proposed that the cyclic nucleotides may affect histamine release at more than one point in the sequence. First, they may regulate the contractility of the microtubles which have been shown to be involved in histamine release. Second, they may influence the state of aggregation and subcellular distribution of the microfilaments which play a role in the maintenance of the normal organization of the cell. As a result of the drop in the cyclic AMP concentration, or the accumulation of lysophosphatides, the cell membrane may be reorganized. This could lead to membrane invagination and an apparent “interiorization” of some of the aqueous milieu. The histamine-containing granules of the mast cells are thus brought into proximity of these deep invaginations by microtubule action, an energy-requiring process. The perigranular membranes fuse with the plasma membrane and the granules exchange their stored histamine for the extracellular sodium which enters the invaginations with the water. The histamine is then equilibrated with the external medium. A number of alternative mechanisms and testable corollaries of the theory are discussed.