In particular, the authors cited a study3 demonstrating that leptin-deficient animals hyperventilate. They are indeed correct that absolute levels of ventilation were higher in these obese leptin-deficient compared with lean wild-type mice. These leptin-deficient mice, however, were not actually hyperventilating since their Paco2 was significantly elevated compared with their lean wild-type control subjects,4 leading us to conclude that they were in fact hypoventilating rather than hyperventilating. Importantly, the observed “excess” in minute ventilation in the ob/ob mice was simply required to keep up with elevations in metabolic load (CO2 production and oxygen consumption) in obesity. This phenomenon is also observed in human obese subjects who produce much more CO2 than their lean counterparts, yet this normalizes after adjusting for body surface area.5 A similar mechanism accounts for the progressive increases in ventilation that were observed in ob/ob leptin-deficient mice3 as they gained additional weight. Conversely, ventilation is further increased when these mice are treated with leptin,3 a finding attributed to increases in hypercapneic ventilatory responses independent of body weight. In conclusion, studies in mice indicate that leptin is a respiratory stimulant, which increases ventilatory drive, and that hypoventilation of leptin-deficient ob/ob mice is reversed with leptin replacement.