We have studied the time course of changes in gas exchange and respiratory mechanics using two different modes of ventilation during 7 h of isoflurane anaesthesia in pigs. One group received conventional control mode ventilation (CV). The other group received biologically variable ventilation (BVV) which simulates the breath-to-breath variation in ventilatory frequency (f) that characterizes normal spontaneous ventilation. After baseline measurements with CV, animals were allocated randomly to either CV or BVV (FIO2 1.0 with 1.5% end-tidal isoflurane). With BVV, there were 376 changes in f and tidal volume (VT) over 25.1 min. Ventilation was continued over the next 7 h and blood gases and respiratory mechanics were measured every 60 min. The modulation file used to control the ventilator for BVV used an inverse power law frequency distribution (I/fa with a = 2.3 +/- 0.3). After 7 h, at a similar delivered minute ventilation, significantly greater PaO2 (mean 72.3 (SD 4.0) vs 63.5 (6.5) kPa) and respiratory system compliance (1.08 (0.08) vs 0.92 (0.16) ml cm H2O-1 kg-1) and lower PaCO2 (6.5 (0.7) vs 8.7 (1.5) kPa) and shunt fraction (7.2 (2.7)% vs 12.3 (6.2)%) were seen with BVV, with no significant difference in peak airway pressure (16.3 (1.2) vs 15.3 (3.7) cm H2O). A deterioration in gas exchange and respiratory mechanics was seen with conventional control mode ventilation but not with BVV in this experimental model of prolonged anaesthesia.