We compared the accuracy and reliability of a validated, physiological simulator and six intensive care specialists in predicting changes in arterial oxygen tension (PaO(2)), arterial carbon dioxide tension (PaCO(2)) and pH following adjustment of mechanical ventilation. Twenty-five data sets were collected before and after routine alterations in ventilator settings. Fractional inspired oxygen was adjusted in all patients and minute volume was adjusted in 13 patients. The simulator was more accurate and consistent than all the physicians in predicting the magnitude of PaO(2) and pH change. The simulator had a larger bias in estimating the magnitude of change of PaCO(2) than four of the physicians, but was more consistent than all but one of the physicians. The simulator may prove to be a useful tool in the management of mechanical ventilation. Incorporation into mechanical ventilators in a passive predictive role or an active 'closed-loop' ventilation management system are potential roles for physiological simulation.