Two indices of the total mechanical load on the ventilatory muscles, i.e., the work per minute (W.min-1) and the inflation pressure time index (PTI), have been developed to better assess muscle energy demands and fatigue potential. However, the relationship of these two indices to the various individual determinants of load and to muscle energy demands and fatigue potential are not well understood. To investigate these relationships in a theoretical fashion, we first constructed a computer model to quantitate the magnitude and relative effects of changes in the ventilation component of load, i.e., alveolar ventilation demands (VA) and dead space volume (VD), and changes in the respiratory system impedance component of load, i.e., compliance (Crs) and resistance (Raw), on W.min-1 and PTI over a wide, clinically relevant, range of ventilatory conditions. From this analysis, we demonstrated that: (1) high mechanical loads could be developed over a wide range of circumstances (i.e., W.min-1 ranged from 0.29 kg.m.min-1 to 30.55 kg.m.min-1 and PTI ranged from 1.22 to 28.8 cm H2O as ventilation increased from 7 to 39 L.min-1 and impedances worsened from normal to a combined restricted and obstructed pattern); (2) each load determinant (i.e., VA, VD, Crs, and Raw) contributed substantially to these two indices of total mechanical load; (3) although impedance changes had comparable effects on W.min-1 and PTI, ventilation changes, as would be expected, had a greater effect on W.min-1 than on PTI.(ABSTRACT TRUNCATED AT 250 WORDS)