1. Experiments on rats were made to find whether the increased liability of the kidney-cortex tubules to autolysis post mortem, which is a well-established abnormality in vitamin E deficiency, can be correlated with changes in lysosomal activity. Parallel observations were made on the development of certain other abnormalities characteristic of avitaminosis E. 2. In rats killed after long periods (8-10 months) of subsistence on a standard vitamin E-deficient diet, containing lard, both the rate of kidney autolysis post mortem and the enzyme activity of lysosome preparations from the fresh tissues were much greater than in controls. A greater percentage difference was usually found in the ;free' enzyme fraction than in ;bound' or ;total' activity. 3. In rats killed after graded periods (3-8 months) of deficiency, two abnormalities (decreased resistance of the erythrocytes to haemolysis, and brown discoloration of the uterus) were already evident at a stage (3-4 months) when the liability to rapid kidney autolysis had not begun. At this point the enzymic activity of kidney extracts differed little between deficient animals and controls given alpha-tocopherol. As the duration of deficiency advanced, parallel increases occurred in the rate of kidney autolysis and in lysosomal instability. 4. When cod-liver oil, rich in polyunsaturated fatty acids but freed from vitamin A, was substituted for lard in the diet, the time (1(1/2) months) required for the inducement of both rapid kidney autolysis and decreased lysosomal stability was greatly shortened. The time for the inducement of brown discoloration of the uterus was not shortened and the kidney abnormalities appeared while the uterus was still normal. 5. Confirmation was thus obtained for the view that the various tissues of the rat respond differently to the relationship between the adequacy of the vitamin E status and the intake of polyunsaturated fatty acids. The kidney-cortex tubules, as evidenced by autolysis post mortem and the corresponding decrease in lysosomal stability, may be classed among those tissues that are most sensitive to the effect of high intakes of polyunsaturated acids.