We studied the discriminative power of the transfer factor (TLCO), KCO (TLCO/Va) and ZCO (a corrected TLCO according to alveolar volume measured (Va), introduced by our group), in order to differentiate diffuse interstitial disease from other restrictive diseases. Measurements were taken in 46 subjects, divided into two groups: Pure restriction (group 1: normal subjects with voluntary restriction and diseased subjects) and (2) diffuse interstitial restriction (group 2). There were no statistical differences in Va between groups 1 and 2. TLCO was statistically lower in groups 1 and 2 in comparison with the control group (normal values of our laboratory in test with Va greater than 90% of predicted) and showed a significant difference when group 1 was compared with group 2. Similar results (but with higher values than those of the control group) were found for KCO. A similar difference exists in ZCO only when group 2 is compared with group 1, but not when group 1 is compared with the control group. The corrected diffusion capacity ZCO yields the highest discriminative power.