By the use of xenon-133 and a scintillation camera with digital data storage and processing system, a topographic relationship between ventilation distribution (V) and perfusion distribution (Q) was examined quantitatively in two groups of normal nonsmokers and one of older smokers, all healthy. In addition, subjects with a variety of cardiopulmonary disease were tested. The fractional regional ventilation (VR) and regional perfusion (QR) were plotted against the V/Q ratio on a logarithmic abscissa for the normal subjects; both were distributed log-normally with a narrow standard deviation, and were dissociated slightly from each other. However, with smoking and with increasing age, the s.d. and the dissociation became wider, suggesting an impairment of gas exchange as estimated by alveolar-atrial gas-pressure differences (A-aD), which were calculated by putting these topographic relationships into a gas-exchange program in a computer. In various cardiopulmonary diseases a good correlation was found between the estimated A-aDO2 thus obtained and the actual A-aDO2 derived from analysis of the blood gases.