The extent to which a single breath measurement represents available gas dilutional as well as compressible thoracic volume in emphysema patients has not been quantified. We therefore measured single breath (TLCSB) and rebreathe helium dilution (TLCRB), and plethysmographic lung volume (TLCpleth), in fifty-five outpatients with clinical and radiographic emphysema, and in twenty-one normal controls. Among emphysema patients, TLCSB increasingly underestimated both TLCpleth and TLCRB as FEV1% predicted decreased (p for interaction=0.001 for both) by a mean of 1.7 l for TLCRB (p<0.001) and 2.2l for TLCpleth (p<0.001). In contrast, TLCRB underestimated TLCpleth by a mean of 0.5l (p<0.001) regardless of FEV1% (p for interaction=0.25). TLCSB, TLCRB, and TLCpleth showed strong agreement among normal subjects. We conclude that TLCSB underestimates available gas dilutional and compressible lung volume as physiologic emphysema severity increases. In contrast, TLCRB and TLCpleth show closer agreement which is unaffected by physiologic emphysema severity.