Pulmonary failure is almost always present in the early or late phase of multiple organ failure (MOF). Acute lung failure (ALF) is a uniquely constant response to direct or indirect insults to the lung. Increased pulmonary microvascular permeability (PMVP) is associated with the onset of lung permeability edema, the hallmark of ALF. The sequence of PMVP and the development of ALF caused by direct insults are studied. METHODS. A series of 255 trauma patients admitted to our intensive care unit (ICU) from 1987 to 1988 were enrolled in this prospective study. ALF was defined as stage III of the Posttraumatic Pulmonary Insufficiency Score; sepsis syndrome, according to Montgomery; organ failure, as stage II of the MOF score, and MOF was recorded when at least two organs had failed. Thoracic injury and aspiration were expected as direct, sepsis and shock alone as indirect insults to the lung. A computerized large field of view gamma camera was used to measure PMVP simultaneously over both lungs by means of 113mIn-transferrin and 99mTc-erythrocytes. The pulmonary microvascular permeability index (PMVPI; %/h) was used to quantify PMVP in the dynamic scintigraphic measurement. RESULTS. Of the 255 trauma patients (ISS = 33.9 +/- 18.7), 21% (52) patients (ISS = 41 +/- 17.8) developed ALF. 50 (or 96%) of the ALF patients developed MOF in addition, and 27 (72%) of the patients with directly induced ALF developed sepsis syndrome later. Direct lung injury was present in 77% (37) of the patients with posttraumatic ALF. Thoracic injury was the main cause of ALF: 58% (30) of 52 patients with ALF had a thoracic injury, which was true of only 30% of the non-ALF group (P less than 0.05). 33 (or 89%) of the ALF patients with direct injury developed ALF less than 72 h after injury (early ALF), and only 11% (4) later than 72 h after injury (late ALF). Indirect injury of the lung was present in 22% (12) of the patients with posttraumatic ALF. Indirectly induced ALF occurred in less than 72 h in 36% (4) and more than 72 h after injury in 64% (7) trauma patients. PMVP was determined in 21 of the 30 patients with thoracic injury. Initial evaluation of these patients with direct induced ALF showed significantly elevated (P less than 0.01) PMVP for the traumatized (PMVPI = 10.8 +/- 5.1%/h) but normal values for the nontraumatized lung (PMVPI = 3.9 +/- 3.4%/h), whereas 4 days later the PMVP increased significantly (P less than 0.05) on the primarily healthy side (PMVPI = 8.0 +/- 5.0%/h) while remaining elevated for the traumatized lung (PMVPI = 10.9 +/- 6.0%/h). In the control group the PMVPI was 2.6 +/- 2.8%/h for the right and 2.0 +/- 2.8%/h for the left lung. Similar values were found in mechanically ventilated ICU patients without ALF. DISCUSSION. Direct injury seems to be the dominant mechanism for early manifestation (less than 72 h) of posttraumatic ALF. The thoracic trauma seems to damage the pulmonary endothelium directly, thus increasing PMVP in a circumscribed region. An overwhelming inflammatory response may cause the later increase in PMVP in the primarily healthy lung areas.