A trial of separation from mechanical ventilation may induce an abnormal respiratory pattern and a maldistribution of ventilation-to-perfusion ratios (VA/Q), especially in patients with chronic obstructive pulmonary disease. This study was designed to assess the effects of three different modes of ventilation on the distribution of global and also regional VA/Q in eight patients with chronic obstructive pulmonary disease recovering from acute respiratory failure who remained dependent on mechanical ventilation after more than 5 days of attempted separation from the ventilator. VA/Q distribution was assessed using the multiple inert gas and isotopic scanning methods after 30 min each of controlled mechanical ventilation (CMV), 10 cmH2O inspiratory pressure support, and spontaneous breathing (SB). Controlled ventilation was provided at a respiratory rate ranging from 12 to 18 breaths per min and a tidal volume of 8 ml.kg-1. In comparison to CMV, SB resulted in a decrease in tidal volume (from 512 +/- 144 to 301 +/- 102 ml, P less than 0.01), and an increase in respiratory rate (from 15.5 +/- 3.2 to 27.3 +/- 15.0 breaths per min, P less than 0.05), which increased dead space (+7.1% of minute ventilation), cardiac output (+36%), and the perfusion to areas of low VA/Q (+8.9% of cardiac output) (P less than 0.05, P less than 0.001, and P less than 0.05, respectively). Isotopic scans revealed a horizontal craniocaudal difference of VA/Q in all modes, with the lowest VA/Q zones at the basal part of the lungs (mean basal VA/Q 0.58 in SB and 1.05 in CMV).(ABSTRACT TRUNCATED AT 250 WORDS)