Respiratory rate (RR) increases as a function of ventilator flow rate (V (over dot)). We wished to determine whether this is due to a decrease in neural inspiratory time (TIn), neural expiratory time (TEn), or both, To accomplish this, we ventilated 15 normal subjects in the assist volume cycled mode. Ventilator flow rate was varied at random, at four breaths with each step, over the flow range from 0.8 (V (over dot)min) to 2.5 (V (over dot)max) L/s. VT was kept constant. The pressure developed by respiratory muscles (Pmus) was calculated with the equation of motion (Pmus = V (over dot) . R + V . E - Paw, where R = resistance, V = volume, E = elastance, and Paw = airway pressure). Electromyography of the diaphragm (Edi) was also done in five subjects. TIn and TEn were determined from the Pmus or Edi waveform. TIn decreased progressively as a function of V (over dot), from 1.44 +/- 0.34 s at V (over dot)min to 0.62 +/- 0.26 s at V (over dot)max (p < 0.00001). Changes in TEn were inconsistent and not significant. TIn/Ttot decreased significantly (0.30 +/- 0.06 at V (over dot)min to 0.18 +/- 0.09 at V (over dot)max; p < 0.00001). We conclude that TI is highly sensitive to ventilator flow, and that the RR response to V (over dot) is primarily related to this TIn response. Because an increase in V (over dot) progressively reduces TIn/Ttot, and this variable is an important determinant of inspiratory muscle energetics, we further conclude that inspiratory muscle energy expenditure is quite sensitive to V (over dot) over the range from 0.8 to 2.5 L/s.