The O2 consumption of the respiratory muscles (VO2resp), work of breathing, and the time integral of the transdiaphragmatic pressure (TTdi) were measured in four normal subjects breathing against inspiratory resistance. A total of 39 runs were performed at mean tidal transdiaphragmatic pressures (Pdi) ranging from 15 to 53 cmH2O, respiratory frequencies from 3.5 to 22 breaths/min, and inspiratory time durations (TI) from 32 to 76% of the total breath duration. Each run was maintained from 8 to 17 min and the above parameters were kept constant by the subject via visual feedback of Pdi and TI with an oscilloscope. Most of the runs (36 of 39) were performed at TTdi values below those known to produce respiratory muscle fatigue. We found a strong linear correlation between the VO2resp and the TTdi (r = 0.74, P less than 0.001) and a weaker correlation between VO2resp and W (r = 0.31, P less than 0.05). These data suggest that TTdi is a good estimator of VO2resp over a wide range of respiratory patterns during inspiratory resistance breathing. The high variability seen in respiratory muscle efficiency during resistive breathing may be due to W not being a good indicator of the energy consumed by the respiratory muscles.