The available clinical information to date does not support the hypothesis that tissue oxygen debt is the primary cause of the wasting process in the chronic obstructive pulmonary disease (COPD) patient population. However, this should not deter the 'believers' of the hypothesis from further investigation. The information outlined above supports the need for reconsideration of this clinical problem. Tissue oxygen requirements and utilization is a complex interplay of multiple variables. Likewise, the assessment of nutritional status in the setting of oxygen therapy is complicated by shifts in body fluid compartments independent of changes in the fat-free mass (FFM). Utilization of newer techniques will be required to resolve the contribution of low tissue oxygenation to the wasting process. The continued development of noninvasive methods for the assessment of tissue metabolism, cardiac function, and tissue energy requirements will allow investigators to further clarify the relationship between tissue oxygenation and metabolism in patients with COPD. Clinical trials designed to examine this issue must recognize the multiple effects of oxygen on all aspects of nutrient utilization, including caloric intake, needs, and tissue delivery. Failure to address all aspects of this system will lead to continued debate regarding the etiology of weight loss in the COPD patient population.