In 12 patients with chronic obstructive pulmonary disease (COPD) receiving pressure support ventilation (PSV), we studied the variability of respiratory muscle unloading and defined its physiologic determinants using a modified pressure-time product (PTP). Inspiratory PTP/min decreased as PSV was increased (p < 0.001), but there was considerable interindividual variation: coefficients of variations of up to 96%. On multiple linear regression analysis, 73 to 83% of the variability in inspiratory PTP was explained by inspiratory resistance, minute ventilation, and intrinsic positive end-expiratory pressure. Taking an inspiratory PTP/min of < 125 cm H2O.sec/min to represent a desirable level of inspiratory effort during PSV, a respiratory frequency of < or = 30 breaths/min was more accurate than a tidal volume > 0.6 L in predicting this threshold (p < 0.001). At PSV of 20 cm H2O, expiratory effort, quantitated by an expiratory PTP, was clearly evident in five patients before the cessation of inspiratory flow, signifying that the patient was "fighting" the ventilator; of note, these five patients had a frequency of < or = 30 breaths/min. In conclusion, patient-ventilator interactions in patients with COPD are complex, and events in expiration need to be considered in addition to those of inspiration.