The purpose of this investigation was to assess the density-dependent flow-volume components of the forced vital capacity using simultaneous spirometry, respiratory inductive plethysmography, and body plethysmography in the detection of small airway disease. The forced vital capacity was measured during air, helium-oxygen and sulfur-hexafluoride breathing to provide a range of gas density influences. Combining flow measured at the mouth with volume referenced to change in alveolar gas volume as measured by body or respiratory inductive plethysmography during helium-oxygen breathing accentuated the differences between nonsmokers and smokers because of the variable degree of alveolar gas compression occurring over the second half of FVC. The volume of isoflow obtained when comparing the helium and oxygen mixture to air also effectively separated nonsmokers from smokers. The utilization of the high density gas mixture, sulfur hexafluoride-oxygen during the FVC maneuver did not provide useful diagnostic information. Therefore, density-dependent flow-volume information using helium as a test gas alone or compared to air with a variety of analyses is a good approach to detection of early lung disease in smokers.