Total lung capacity (TLC) and residual volume (RV) measurements derived from multi-breath and single breath helium dilution methods were combined to produce four indices of gas mixing: single breath volume/multi-breath volume ratio (TLCr, RVr) or multi-breath volume minus single breath volume difference (TLCd, RVd). The reproducibility of these indices and their sensitivity and specificity in discriminating between normal subjects and those with mild asthma and severe chronic obstructive pulmonary disease (COPD) was assessed. The total lung capacity ratio (TLCr) was the superior variable overall, providing a single range for both sexes with a specificity and sensitivity similar to that of the forced expiratory volume in one second (FEV1) in the diagnosis of airflow obstruction. Despite the similar sensitivity, correlation between TLCr and FEV1 was only moderate (r = 0.56). This may reflect greater influence of peripheral rather than central airflow obstruction on TLCr. Combining both tests improved sensitivity in the detection of airways obstruction in the asthmatic and COPD groups studied.