Chest wall inertance (Iw) constitutes a mechanical load which is small in normal individuals, but increases in the morbidly obese. The effect of increased Iw on respiratory drive and pattern has not previously been investigated. We studied this effect by measuring rebreathing CO2 response in 10 normal subjects with and without a 45.5 kg inertial load. Changes in inspiratory occlusion pressure (P0.1), ventilation, respiratory rate, mean inspiratory flow (VT/TI) duty cycle (TI/TT), inspiratory and expiratory times, and [P0.1/(VT/TI)] were assessed. The P0.1 vs. PETCO2 response shifted to the left during inertial loading, while the slope remained unchanged (x-intercept = 36.7 +/- 4.9 mm Hg unloaded vs. 32.7 +/- 7.5 mm Hg loaded, P less than 0.05), increasing P0.1 from 18.5 +/- 8.0 to 21.0 +/- 7.6 cm H2O at PETCO2 = 6.5 mm Hg (P less than 0.005). Respiratory pattern was unchanged with the inertial load except for a slight decrease in tidal volume. The inspiratory transfer characteristic [P0.1/(VT/TI)] at PETCO2 = 65 mm Hg increased significantly (8.3 +/- 2.0 to 10.5 +/- 2.9 cm H2O.(L.sec-1)-1, P less than 0.025) illustrating the strategy of maintaining similar ventilation by increasing inspiratory force against the load.