We quantified inspiratory effort during patient-triggered ventilator cycles in 20 critically ill patients receiving assisted mechanical ventilation (AMV). An index of the patient's work per liter of ventilation (WP) was defined as the difference in the mechanical work done by the ventilator during controlled and assisted breathing cycles at similar settings of tidal volume and flow. WP was estimated graphically from plots of airway pressure against inflation volume for peak flow settings of 60 L/min and 100 L/min. During patient-initiated cycles, effort did not cease with the onset of gas delivery. Values for WP varied widely but at both flow settings frequently equalled or exceeded the total workload expected for a spontaneously breathing normal subject. Furthermore, the patient's component of the mechanical workload during AMV was often a large percentage of the work performed during spontaneous breathing 30 s after discontinuing ventilator support (at 60 L/min: mean 62.6%; range 30.3 to 116.3%). The addition of deadspace to the external circuit increased V̇E and WP significantly. Both the maximally negative pressure generated against an occluded airway and the deflection of esophageal pressure in the first 100 ms after the onset of inspiratory effort were highly correlated with WP, suggesting the importance of strength and ventilatory drive as determinants of patient effort. WP correlated poorly with measures of chest mechanics, and there was no separation of WP values for the two flow rates we studied, perhaps because both settings exceeded the patient's spontaneous demand for airflow (FD). Reducing the rate of gas delivery below FD (to 40 L/min) increased WP in 5 additional subjects. We conclude that significant exertion of the respiratory musculature persists throughout patient-initiated ventilatory cycles, often to levels which could tax the ventilatory reserve. Increased awareness of this phenomenon and its determinants may allow more appropriate selection of the ventilation mode and machine settings chosen for ventilatory support.