Measurements of gas exchange have been demonstrated to be clinically useful in the care of critically ill and malnourished patients. Using principles of indirect calorimetry, resting energy expenditure (REE) can be calculated from gas exchange data and used as the basis for designing a nutritional support regimen as well as for following the patient's metabolic state. This study demonstrates that a relatively minor procedure, such as percutaneous muscle biopsy, can induce temporary but major increases in gas exchange and lead to an overestimation of REE. Four studies were performed on 3 healthy adult subjects admitted to the Surgical Metabolism Unit for nutritional study. A percutaneous muscle biopsy was performed with the subject inside a canopy with continuous recording of oxygen consumption (Vo2) and carbon dioxide production (Vco2). After the muscle biopsy, Vco2 and Vo2 increased 93 and 103% (at their peak value), respectively. The mean duration that these changes persisted at least 15% above control was 10.6 ± 7.8 (SD) and 11.4 ± 5.9 min of Vco2 and Vo2, respectively. Thus, considerable artifacts in the estimation of REE can occur due to painful stimuli.