The combination of functional indices best reflecting the extent of emphysema is not known. High-resolution computed tomography (HRCT) studies of 106 patients with emphysema [men=71; median age=61 (range=26-86 years)] were reviewed and the extent of emphysema was quantified: (a) visually (emphysema(vis)) and (b) by automated estimation (emphysema(auto)). Functional-morphologic relationships were compared for the two scoring systems, and a composite physiologic index (CPI) (providing the best fit of functional indices against emphysema extent) was derived. Emphysema(vis) and emphysema(auto) were strongly correlated (r=0.90; p<0.0005), but the extent of emphysema(vis) was consistently greater (p<0.00005). Emphysema(vis) correlated most strongly with indices of gas transfer [percent predicted single-breath carbon monoxide diffusing capacity (Dl(co)) and alveolar volume (K(co)); r=-0.70, both p<0.0005]. The combination of physiologic indices most representative of emphysema extent on CT (using visual or automated methods) consisted of K(co) and forced expiratory volume in 1 s (FEV(1)) levels. The equation explanatory power was higher for visual scoring [emphysema(vis)=96.8-(0.67 x % predicted K(co))-(0.41 x % predicted FEV(1)); equation r(2)=0.57] than automated estimation (equation r(2)=0.48). Weighted combinations of K(co) and FEV(1) levels provide a CPI best reflecting morphologic emphysema extent. CPI has the potential to refine the stratification of patients in epidemiological and therapeutic studies.