The analysis of the gas in a single expirate has long been used to estimate the degree of ventilation-perfusion (A/) inequality in the lung. To further validate this estimate, we examined three measures of A/ inhomogeneity calculated from a single full exhalation in nine anesthetized mongrel dogs under control conditions and after exposure to aerosolized methacholine. These measurements were then compared with arterial blood gases and with measurements of A/ inhomogeneity obtained using the multiple inert gas elimination technique. The slope of the instantaneous respiratory exchange ratio (R slope) vs. expired volume was poorly correlated with independent measures, probably because of the curvilinear nature of the relationship due to continuing gas exchange. When R was converted to the intrabreath A/ (i/), the best index was the slope of i/ vs. volume over phase III (i/ slope). This was strongly correlated with independent measures, especially those relating to inhomogeneity of perfusion. The correlations for i/ slope and R slope considerably improved when only the first half of phase III was considered. We conclude that a useful noninvasive measurement of A/ inhomogeneity can be derived from the intrabreath respiratory exchange ratio.