AbstractIn a long‐term multigeneration study, conducted in our laboratories for 32‐years, with occasional longevity and histopathological evaluations included, rats of our own inbred strain (originally of Wistar derivation) were fed semisynthetic diets comprising whole wheat, skim milk powder, and fat in the form of margarine products. The total source of tocopherols was the dietary fat itself. Saturated fatty acid content (S) remained relatively constant at about 20% of the fat and total tocopherol level also remained constant at about 0.12% of the fat. Polyunsaturated fatty acid (P) content, however, progressively increased almost fourfold, from 7.5% to 28.5% and alphatocopherol levels decreased to one‐half level, from 0.033% to 0.016% of the fat. Hence, the ratio of polyunsaturated fatty acids to alpha‐tocopherol content changed markedly from 227∶1 to 1780∶1, with other factors (relative to fat composition) held constant during the 32‐year period of feedings and observations. Fat level in the diet increased over the years from 9.2% to 16.0% or from about 21% to about 33% of the caloric intake. Thus, quality and quantity of the fat in the diet progressively changed, and the impact of these changes was evaluated by comparing biological performances of the successive generations. Growth and reproduction and lactation performances were noted to be regularly satisfactory and comparable from generation to generation throughout the experimental period. Longevity studies conducted on arbitrarily selected generations also provided data showing no deleterious effects associated with a dietary change. Histopathological examinations of tissue revealed minimal myocarditis and no malignant tumors which could be attributed to a dietary factor. No vitamin E deficiencies were observed. Even the in vitro peroxide hemolysis values for the red blood cells of the animals, fed the diets containing the higher levels of polyunsaturated fatty acids, were low, indicating that the dietary fats provided sufficient absorbable tocopherol to protect the potentially oxidizable unsaturated fatty acids in the erythrocyte membrane. Biochemical data reflected responses to aging and not to any specific diet fed. It is concluded that a diet providing as much as 33% of the calories as a fat, the latter containing up to 28.5% polyunsaturated fatty acids, substantially of the essential fatty acid type, with a P/S ratio of up to 1.6∶1 and a polyunsaturated fatty acid to alphatocopherol ratio as high as 1780∶1] produces no undesirable effects in the rat.