The measurement of body composition by multiple isotope dilution provides an accurate and precise measure of both the nutritional state and the response to nutritional support. A multiple isotope dilution technique has been developed that permits measurement of the three major components of body composition: body fat, extracellular mass (ECM), and body cell mass (BCM). Normal body composition was defined by data obtained in 25 healthy volunteers. Malnutrition is characterized by a loss of BCM and an expansion of the ECM, and as a result the lean body mass is not significantly different from normal. The loss of body weight with malnutrition therefore often reflects the loss of body fat. The utility of body composition measurements was demonstrated by determining the effect of total parenteral nutrition on body composition to determine the relationship between caloric intake and the change in the BCM. A statistically significant relationship was developed which demonstrated that a caloric intake in the range of 30-40 cal/kg/day is required for maintenance. To restore a depleted or malnourished BCM requires a caloric intake in excess of that required for maintenance. The measurement of body composition by multiple isotope dilution is complex and time consuming, and requires specialized laboratory facilities and specially trained personnel. As a result, these measurements are not suited for routine patient management, but should rather be reserved for research purposes.