Although impairment of gas exchange caused by ventilation-perfusion (VA/Q) mismatch has been extensively analyzed, there have been no systematic studies focused on determining the distributions of diffusion properties in dose connection with those of VA/Q. We attempted to clarify the simultaneous distributions of VA/Q and diffusion capacity to perfusion (D/Q) in patients with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD). To assess pathologic determinants causing functional abnormalities, we compared VA/Q and D/Q distributions with the findings on high-resolution computed tomography. O2, CO2, and CO together with six foreign inert gases were used as indicator gases. We transformed the measured data on indicator gases in arterial blood into a continuous distribution of Q in the VA/Q-D/Q field. In IPF, active alveolitis or acinitis played a major role in producing low D/Q regions impeding gas exchange via a diffusion limitation, whereas extensive fibrosis with minimal inflammation accounted for low D/Q as well as low VA/Q regions. In COPD, no regions with low D/Q ratios were observed, but an abnormality in the VA/Q distribution with low or high VA/Q ratios was identified. Emphysematous lesions produced high VA/Q regions, whereas peripheral airway involvement yielded low VA/Q regions. These findings suggest that hypoxemia in patients with IPF is caused by inhomogeneous distributions of D/Q in combination with those of VA/Q. Hypoxemia in patients with COPD is attributable primarily to inhomogeneities in VA/Q rather than in D/Q distributions.