The alveolar deadspace as a fraction of alveolar ventilation (VDalv/VTalv), while technically difficult to measure, is an objective monitor of pulmonary disease progression and a predictor of successful weaning from mechanical ventilation. The aim of the study was to examine the relationship between the arterial to end-tidal PCO2 gradient (Pa-E'CO2) and VDalv/VTalv and between (Pa-E'CO2)/PaCO2 and VDalv/VTalv using the Nottingham Physiology Simulator, an original, validated physiology simulation. The relationships were observed while pulmonary shunt, anatomical deadspace, ventilatory minute volume and metabolic rate were varied. The relationship between Pa-E'CO2 and VDalv/VTalv was non-linear and was affected significantly by all the factors except anatomical deadspace. The relationship between (Pa-E'CO2)/PaCO2 and VDalv/VTalv (best fit: VDalv VTalv = 1.135 x (Pa-E'CO2)/PaCO2-0.005) during normal physiological conditions was approximately linear and less influenced by physiological variation. Shunt and anatomical deadspace caused some inaccuracy, although they are unlikely to prevent the clinical usefulness of this formula.