Mast cells are the primary effector cells of immediate hypersensitivity reactions in humans. Upon mast cell activation both preformed and newly synthesized mediators are secreted. Histamine can be measured by fluorometric assays, radioenzymatic assays, and immunoassays. These methods have been applied to plasma and urine to detect histamine that had been released in vivo and to release histamine in vitro from basophils and mast cells. Another mast cell constituent is tryptase, which is a more selective marker of mast cells, because negligible amounts are found in basophils. beta-Tryptase is stored in secretory granules and is actively released when mast cells degranulate. alpha-Protryptase remains in the proenzyme form and is constitutively released from mast cells, and consequently its level in serum reflects total numbers of mast cells. alpha-Protryptase levels are elevated in serum at baseline in subjects with systemic mastocytosis, whereas beta-tryptase is elevated in serum from subjects with systemic anaphylaxis. These markers serve as precise clinical indicators of the involvement of mast cells in human disease.