The present study was undertaken in order to describe the morphological differences between pulmonary lesions in acute respiratory distress syndrome originating from direct pulmonary injury (ARDSp) and those originating from extrapulmonary injury (ARDSexp). We investigated a total of 38 ARDS-patients (27 males) ranging in age from 19 to 75 years, classified according to underlying disease in pulmonary (ARDSp) and extrapulmonary disease (ARDSexp). The extent of acute diffuse alveolar damage was assessed morphometrically on histologic gross sections in the upper and lower lobes of one lung. The lesions showed quantitative differences in extent and distribution according to underlying disease (primary pulmonary or secondary involvement). In pulmonary ARDS, a predominance of alveolar collapse (16.6%+/-12.3% versus 10.3%+/-11.9%, p = 0,03), fibrinous exudate (1.7%+/-3.2% versus 0.4%+/-1.1%, p = 0.01) and alveolar wall edema (11.2%+/-7.4% versus 6.6%+/-4.4%, p = 0,05) were found compared to extrapulmonary ARDS. We conclude that the morphology of acute diffuse alveolar damage (DAD) is mainly determined by underlying disease (pulmonary ARDS or extrapulmonary ARDS) differing in quantitative terms within the lung. Physiological, radiographic and respiratory system mechanics differences described in ARDSp and ARDSexp may therefore be due to morphometric differences in pulmonary lesions.