Simultaneous forearm and leg metabolic exchange studies were performed to compare metabolic exchange and change in metabolic activity over time across the forearm and calf skeletal muscle beds in response to nutritional treatment. Seven postoperative upper-gastrointestinal resection patients received intravenous nutrition (IVN) for 10 days. Immediately before IVN was begun, simultaneous ipsilateral forearm and calf blood flow with arterial and venous sampling for plasma glucose and free fatty acids (FFAs), and whole-blood glycerol, lactate, pyruvate, and nitrogen were measured. After 10 days of IVN, these parameters were repeated in carefully standardized steady-state conditions. Although there were no differences between the arm and the leg with mean flux measurements, correlation of arm and leg flux values were only significant for FFA (p < 0.01) and blood nitrogen (p < 0.05). Forearm and leg metabolic exchange results were not in sufficient agreement to permit reliable use of these results interchangeably for individuals. Errors in blood flow measurement appear to be a major determinant of the poor relationship between forearm and leg flux measurements (limits of agreement 3.32-4.72 ml.dl-1 tissue.min-1). In conclusion, both forearm and leg metabolic exchange studies can be used to show the metabolic effects of treatment when groups of subjects are studied, but variability of the methods used result in poor agreement for the measurements of an individual.