Inpatient metabolic studies of human subjects were performed to obtain data on important nutritional issues. It was shown that wide variations in the ratio of carbohydrate to fat do not alter total 24-h energy need. Studies of the fatty acid composition of plasma low-density lipoproteins during low-fat feeding indicated that there can be considerable lipogenesis from carbohydrate in humans during isoenergetic feeding. The energy cost of this conversion must be small or be counterbalanced by other changes in energy metabolism because measured energy need was unaltered by fat-to-carbohydrate ratios. Energy need was, however, markedly varied by changes in body weight. Subjects at their usual body weights who had experimentally induced increases in body weight became inefficient and required a higher energy intake for weight maintenance. The reverse occurred with a reduction in body weight. The set point at which energy storage is defended is clearly different in obese persons.