Preferential localization of pathologic conditions in the upper lobes of the lung might seem unexpected, considering that both blood flow and ventilation predominate in the lower lobes. The erect lung is marked by striking regional non-uniformity in perfusion, ventilation, lymphatic flow, metabolism, and mechanics. These regional disparities form the foundation for a physiologic approach to the evaluation of diffuse lung disease. The pathologic-physiologic correlations in apical lung disease are examined, and a differential diagnosis is offered. Analysis of diffuse lung disease on the basis of radiologic-physiologic correlation is suggested as an aid in radiographic interpretation.