Whole room indirect calorimeters are among the most accurate devices for measurement of human energy expenditure and have provided useful data about determinants of total daily energy expenditure. However, a limitation of whole room indirect calorimeters has been the inability to detect acute (usually <10-15 min) changes in energy expenditure. This precludes using these devices to study the acute effects of food, drugs, or exercise on energy expenditure. We describe modifications made to our whole room indirect calorimeter (respiratory chamber) to allow accurate measurement of energy expenditure over time periods as short as 1 min. The modifications involve changes in the system design and use of signal processing techniques. With these modifications, we can measure energy expenditure in 1-min intervals throughout the day. This allows accurate study of the acute effects of food, exercise, or drugs on energy expenditure in subjects moving freely inside the respiratory chamber. The ability to use respiratory chambers for these types of studies should improve our understanding of how body weight is regulated.