The histochemical nature and the biologic characteristics of the specific cytoplasmic granulations of the juxtaglomerular (J-G) cells of the kidney have been reinvestigated. In the rat, it appears that these cells are mesenchymal in origin and capable of reacting as part of the reticuloendothelial system when exposed to the action of long-chain polymers like dextran or ovomucoid.The substance contained in the granules is probably constituted by a mixture of polysaccharide sulfate esters and lipoids, accounting for their staining properties with metachromatic dyes. Hyaluronic acid is not responsible for the latter reaction.The J-G granules respond in a manner strikingly similar to that of mast-cell granules after treatment with dextran or ovomucoid. The attempt to quantitate the amount of histamine liberated by degranulation of J-G cells has been less successful than with degranulated connective tissue mast cells, owing to the low J-G cell/parenchyma ratio in the kidney.The presence of mast-cell-like elements at the vascular pole of the kidney glomerulus is stressed in view of their possible role in the functional activity of the nephron, owing to the fact that degranulation of these cells is capable of releasing anticoagulant and vasoactive substances like heparin, histamine, and serotonin proximal to 1 of the most important circulatory districts of the body.The finding of elements with analogous characteristics in the subintimal layer of arterioles in other organs raises the question as to whether J-G cells play a less specialized role in the kidney than hitherto supposed.