Nonspecific esterase, and in some cases a "Tween" lipase, were investigated histochemically in arteries and several other tissues of rats and rabbits under various conditions known to affect the development of atherosclerosis: age and sex differences, endocrine and metabolic factors (sex steroids, thyroid function, alloxan diabetes, and fasting), arterial injury, and acute and chronic lipemia. A study of the above enzymes was also made in atherosclerotic rabbit and human aortae. Of the several nonvascular tissues studied, only the enzymes of the male gonads and a male accessory sex organ (the prostate) were influenced by some of the experimental conditions tested: maturation greatly increased the activity of both enzymes in the Leydig cells of the testis, and stilbestrol markedly diminished the esterase activity in the prostate epithelium. Thus, in certain reproductive organs, the enzymes reflected the functional state of the cells under investigation. The following findings were made concerning the enzymes of the arterial wall: 1. Neither of the enzymes was influenced by ageing or sex difference in the rat, rabbit or human. 2. Neither of the enzymes was influenced by sex hormones, acute or chronic lipemia, or any of the metabolic conditions studied in the rat. 3. Esterase disappeared from the foci of acute arterial injury induced by Calciferol treatment in the rat and did not reappear six weeks after infliction of the injury. 4. Strong esterase activity appeared in the cytoplasm of lipo-phages within both human and experimental rabbit atherosclerotic lesions, in contrast to the normal arterial wall which exhibited no esterase activity at all in either species with the methods used. 5. Esterase was absent from the superficial fibrous cap of the human atherosclerotic lesion. It is concluded that: In the rat arteries, which normally exhibit appreciable esterolytic activity, this enzyme appears to be quite stable since it is not visibly modified by ageing or a series of endocrine and metabolic influences; it is, however, drastically diminished by acute vascular injury and this may account, at least in part, for the well known preferential accumulation of lipids in foci of acute arterial damage. In the rabbit arteries, which normally exhibit no histochemically demonstrable esterase, appreciable esterolytic activity appears only within the cytoplasm of cells that have taken up lipid after exposure to chromic lipemia (foam cells of atheromata). Similarly, in human atheromata esterase appeared only in foam cells and was absent from the fibrous cap of the atherosclerotic lesions; thus the absence of lipid from the cap cannot be attributed to increased enzyme activity in this part of the lesion. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate