In 7 normal subjects, mouth occlusion pressure was evaluated as an index of neural drive to the respiratory muscles during CO2 rebreathing, with and without the addition of 2 degrees of elastic loads. During control and loaded rebreathing, changes in both mouth occlusion pressure and ventilation were linearly related to changes in end-tidal PCO2. With elastic loading, the slope of occlusion pressure versus end-tidal PCO2 response consistently increased from control values in all subjects and was greater with the higher load in 6 of 7 subjects. The ventilatory response to elastic loading was variable and inconsistent owing to the variable increase in frequency of breathing, the tidal volume always being diminished. In normal subjects, both mouth occlusion pressure and ventilation appeared to assess neural drive to the respiratory muscles in response to CO2 rebreathing; with elastic loading, only occlusion pressure continued to reflect neuromuscular output. This increased pressure response could have been mediated by neural reflex and/or intrinsic muscle mechanisms. The data suggest that mouth occlusion pressure may be a useful parameter for evaluating neuromuscular control mechanisms under conditions of increased lung elastance.