We investigated the effects of body mass index (BMI) on functional residual capacity (FRC), respiratory mechanics (compliance and resistance), gas exchange, and the inspiratory mechanical work done per liter of ventilation during general anesthesia. We used the esophageal balloon technique, together with rapid airway occlusion during constant inspiratory flow, to partition the mechanics of the respiratory system into its pulmonary and chest wall components. FRC was measured by using the helium dilution technique. We studied 24 consecutive and unselected patients during general anesthesia, before surgical intervention, in the supine position (8 normal subjects with a BMI < or = 25 kg/m2, 8 moderately obese patients with a BMI >25 kg/m2 and <40 kg/m2, and 8 morbidly obese patients with a BMI > or = 40 kg/m2). We found that, with increasing BMI: 1. FRC decreased exponentially (r = 0.86; P < 0.01) 2. the compliance of the total respiratory system and of the lung decreased exponentially (r = 0.86; P < 0.01 and r = 0.81; P < 0.01, respectively), whereas the compliance of the chest wall was only minimally affected (r = 0.45; P < 0.05) 3. the resistance of the total respiratory system and of the lung increased (r = 0.81; P < 0.01 and r = 0.84; P < 0.01, respectively), whereas the chest wall resistance was unaffected (r = 0.06; P = not significant) 4. the oxygenation index (PaO2/PAO2) decreased exponentially (r = 0.81; P < 0.01) and was correlated with FRC (r = 0.62; P < 0.01), whereas PaCO2 was unaffected (r = 0.06; P = not significant) 5. the work of breathing of the total respiratory system increased, mainly due to the lung component (r = 0.88; P < 0.01 and r = 0.81; P < 0.01, respectively). In conclusion, BMI is an important determinant of lung volumes, respiratory mechanics, and oxygenation during general anesthesia with patients in the supine position. CONCLUSIONS The aim of this study was to investigate the influence of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia.