The present study was undertaken in order to describe the local distribution and temporal course of pulmonary lesions in severe ARDS. We investigated a total of 35 patients (22 females), ranging in age from 2 to 51 years, who suffered from ARDS III and IV and were treated by extracorporeal CO2 removal and low frequency positive pressure ventilation (ECCO2-R). The extent of acute and chronic diffuse alveolar damage was assessed on histologic gross sections in the ventral, central and dorsal zone of the upper and lower lobes. The lesions showed a characteristic uniform distribution. Areas with chronic DAD were predominantly situated in the ventral portions of the upper lobes. Acute DAD predominated in the dorsal and basal areas of the lung. The extent of acute and chronic DAD was virtually independent of the duration of disease. Hemorrhage occurred at the interface zone between chronic and acute DAD and made up a significant volume portion of the lung tissue, ranging between 8% (lower lobes) and 42% (upper lobes). We conclude that the progression of acute DAD to chronic DAD is mainly determined by local factors (hydrodynamic and hydrostatic forces, intraalveolar pressure) that differ within the lung, whereas the duration of disease plays a minor role. Parenchymal hemorrhage occurs at the interface between areas of acute and chronic DAD and may therefore primarily be due to an increased susceptibility of the pulmonary parenchyma to mechanical stress.