Nutritional support of the patient with respiratory failure may play a key role in recovery. Nutritional intake not only indirectly influences lung function by altering body composition and most defense mechanisms but interacts directly with respiratory function in a variety of ways. This review will focus on 2 such interactions; the effect of glucose on CO2 production and the effect of protein on ventilatory drive. Glucose administration results in increases in CO2 production via 2 mechanisms; 1) a thermogenic effect and 2) an increase in the respiratory quotient (RQ). In the hypermetabolic, acutely ill patient, both the thermogenic effect and the rise in the RQ contribute to the rise in CO2 production. In the malnourished patient, a rise in the RQ is the primary mechanism for the increase. In either case, the increased need for CO2 elimination results in an increase in ventilatory demand which may precipitate respiratory distress in a patient with previously compromised pulmonary function. Infusions of amino acids, either alone or as a part of a complete nutritional support regimen, results in an enhanced ventilatory response to CO2. This seems to be a result of the thermogenic effect of protein and an increase in the ratio of the plasma concentration of the large amino acids to tryptophan. We postulate that brain uptake of tryptophan which is a precursor to serotonin (a known respiratory inhibitor) is reduced by the presence of increased amounts of the large neutral amino acids that compete with tryptophan for transport across the blood brain barrier, thereby resulting in respiratory stimulation.