We propose to study the physiology and pathophysiology of lung function with particular emphasis on the non-uniformity of ventilation, diffusion and perfusion. Multiple breath studies of inhaled tracers will be employed in computer simulations and actual tests in normal subjects and patients. Computer models of non-uniformities caused by a series of pathological conditions will be written and evaluated to assess the sensitivity of various tests to different types of non-uniformity and to determine pathologies which are compatible with data we and others have collected. Optimized test methods as determined from the models will be compared to the results of similar testing of normal humans and patients. We will seek to specify which results are compatible with proposed pathophysiological causes which lead to non-uniform lung function. Tests to be studied include multiple breath washin and washout of insoluble tracers (N2 argon, He, SF6), transient, studies using C180 and transient studies using inhaled soluble tracers such as N2, Dimethyl ether, halothane, etc. In addition to employing resting breathing patterns, we will examine the effects of frequency and lung volume changes. We will also label different portions of the inspiratory cycle to study the distribution of inspired gases.