THE granular basophil cells of the tissues were first clearly described by Paul Ehrlich (1) and named" mast cells" in the belief that the characteristic metachromatic granules develop in certain mesenchymal cells under conditions of hypernutrition (2). As Ehrlich observed, the cells are common in the loose connective tissues, especially near small blood vessels. Sixty years later Scandinavian workers showed that the metachromatism of the mast cell granules is due to heparin (3), a finding that has since received substantial support from the high anticoagulantactivity of pathological tissues abnormally rich in mast cells (4, 5). It thus seemed that" one of the old problems of histologists, the riddle of the metachromatic gran-ules in the mast cells of Ehrlich" has been solved (6). One curious anomaly remained. It had been known for long that in certain shock states in the dog not only heparin (7) but also histamine (8) is released in quantity from the liver. With this in mind a series of investigations was undertaken to re-examine the status of the mast cellin relation to the tissues and to determine what, if any, is its role in theelaboration and release of histamine.

It was first observed (9) that the granules in somne of the mast cells of the rat stain positively for alkaline phosphatase and the suggestion was made that the enzyme may be concerned in the formation of the metachromatic material by which mast cells are generally recognized. A further study of conditions in the rat (10) supports the idea that these phosphatase-positive mast cells are youngcells whose chief source of origin is from undifferentiated mesenchymal precursors in the adventitia of small blood vessels. However, in the rat such vessels often have one or more muscle coats and as the mast cells mature they tend to migrate away from the vessels into the tissues and there slowly lose their granules. Any secretion from the mature cells must thus permeate the tissues before it enters the blood.