1 Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly in¯ammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and speci®c antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-in¯ammatory molecules that include histamine, cytokines and proteolytic enzymes. 2 Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory eect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell`stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed o, while the eect of cromolyn was limited by rapid tachyphylaxis. 3 Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this eect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo-and monosaccharides were not as eective as the polysaccharides. 4 Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes.5 Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications.