In 16 critically ill patients the arterial-alveolar N2 difference and data from the multiple inert gas elimination technique (MIGET) were compared in the evaluation of the contribution of low alveolar ventilation-perfusion ratio (VA/Q) lung regions (0.005 less than VA/Q less than 0.1) to venous admixture (Qva/QT). The arterial-alveolar N2 difference was determined using a manometric technique for the measurement of the arterial N2 partial pressure (PN2). We adopted a two-compartment model of the lung, one compartment having a VA/Q of approximately 1, the other being open, gas filled, unventilated (VA/Q = 0), and in equilibrium with the mixed venous blood. This theoretical single compartment represents all lung regions responsible for the arterial-alveolar N2 difference. The fractional blood flow to this compartment was calculated using an appropriate mixing equation (Q0/QT). There was a weak but significant relationship between Q0/QT and the perfusion fraction to lung regions with low VA/Q (0.005 less than VA/Q less than 0.1) (r = 0.542, P less than 0.05) and a close relationship between Q0/QT and the perfusion fraction to lung regions with VA/Q ratios less than 0.9 (r = 0.862, P less than 0.001) as obtained from MIGET. The difference Qva/QT-Q0/QT yielded a close estimation of the MIGET right-to-left shunt (Qs/QT) (r = 0.962, P less than 0.001). We conclude that the assessment of the arterial-alveolar N2 difference and Q0/QT does not yield a quantitative estimation of the contribution of pathologically low VA/Q areas to QVa/QT because these parameters reflect an unknown combination of pathological and normal (0.1 less than VA/Q less than 0.9) gas exchange units.(ABSTRACT TRUNCATED AT 250 WORDS)