The effect of high-fat vs high-carbohydrate diets on the pentose cycle (PC) in rats has been partially clarified. Rats show a high activity of glucose-6-phosphate dehydrogenase, the iniltial enzyme in the cycle, when their diet is high in carbohydrate and adequate in protein. Substitution of fat for carbohydrate in the diet lowers the level of this enzyme (1-3) and also reduces the amount of glucose available for catabolism by any pathway. I t is not clear how the dietary ratio of fat to carbohydrate affects the fraction of glucose catabolism occurring by way of the PC.In the present studies, the relative role of the pentose cycle in glucose catabolism was studied by measuring expired 14C02 after the injection of glucose labeled at various sites. Observations were made during the feeding of high-fat vs high-carbohydrate diets under conditions in which caloric intake, physical activity, and kind of dietary carbohydrate were varied. Since rat strains are known to differ in tissue levels of glucose-6-phosphate dehydrogenase (4) and appear to vary in their use of the pentose cycle, two strains were used in the present study.Methods. Treatment of Animals. The present studies were carried out in two stages with approximately 1 50-day-old male rats 1Since the first portion of this study was completed, R.A.A. has been in the Department of Food, Nutrition and Institution Administration, University of Maryland. 2 The data for the second portion of this study are from a thesis by Y.L.A. submitted to the Graduate School, University of Maryland, in partial ful'fdlment of the requirements for the MS degree.which had been eating a commercial stock diet.3 Animals were then given, for 6 or 8 weeks, either a high-fat or high-carbohydrate diet. These diets (5, 6) contained the same adequate quantities of protein, vitamins, and minerals per calorie and provided either 12 or 54% of metabolizable calories as carbohydrate and, respectively, 62 or 20% as a 3: 1 mixture of beef tallow and corn oil. At intervals during the experimental diet period, a total of five animals per treatment group were injected intraperitoneally with l-14Cglucose, 6-14C-glucose, or uniformly labeled U-'4C-glucose. Each rat received about 1 pCi of radioactivity in not more than 1 pmole of glucose. Expired COZ was collected over two successive 6 hr intervals and analyzed for.l4CO2, as previously described (7).In the first study, the animals used were from a Wistar-derived strain. The carbohydrate provided in the high-and low-fat diets was cornstarch. All animals were fed once daily in the early morning. Half the animals were offered more than they would eat, while the other half were restricted to 65% of the ad libitum intake. Half the animals subjected to each of the four dietary regimens were forced to swim twice daily for 30 min in 37' water for a total of 1 hr/day; while the remaining half were left undisturbed in their separate cages.The second study dealt with ad libitum fed Sprague-Dawley rats. The carbohydrate, consisting either of sucrose, lactose, raw c...