Five obese women were fed for six successive 5-day periods 400 kcal from single energy sources and 800 kcal combinations of these. At 400 kcal/day, ketosis was least with carbohydrate and greatest with fat as the diet. Four hundred kcal exogenous protein per day, without any other dietary energy source, was found to reduce the degree of ketosis. The addition of 400 kcal exogenous carbohydrate to 400 kcal protein was found effectively to prevent the development of ketosis in the obese, but addition of 400 kcal as fat was not beneficial. As has been previously observed, serum uric acid was found to rise and urinary uric acid to fall in obese subjects on lowcalorie, high-fat diets. A low-calorie, high-carbohydrate diet had the reverse effect. Loss of weight, sodium, and potassium was much greater with diets based on fat than on carbohydrate. Four hundred kcal carbohydrate per day had a greater protein-sparing effect than 400 kcal fat per day in obese women. There appeared to be adaptation to continued low-calorie intake, evidenced by progressively less negative nitrogen balances in successive periods. In the last period, one subject maintained positive balance with only 400 kcal, as protein. We conclude that carbohydrate is necessary in the diet to prevent ketosis and loss of cations, to spare tissue protein and to promote adequate clearance of uric acid, when endogenous fat is the chief source of energy. Exogenous protein can fulfill part of this function, but it is less effective than carbohydrate at equivalently low calorie intakes. © 1969.