1. The aim of the study was to determine the role of increased microvascular protein permeability, as measured by the 67gallium (Ga)-transferrin pulmonary leak index, in pneumonia and associated adult respiratory distress syndrome (ARDS). 2. Eighteen consecutive patients with microbiologically confirmed pneumonia (radiographic infiltrates, purulent sputum) and needing respiratory monitoring (n = 2) or mechanical ventilation (n = 16) in the intensive care unit were studied prospectively. The pulmonary leak index using 67Ga-transferrin and 99mTc red blood cells was measured with a mobile probe system over both lung apices (normal value below 14.1 x 10(-3) min-1) within 72 h of intensive care unit admission, and the lung injury score was calculated from radiographic, ventilatory and lung mechanical data. 3. Patients with pneumonia (lung injury score < 2.5, n = 10) had a lower (P < 0.01) pulmonary leak index, averaged for both lungs, with a median of 23.9 [range (7.0-47.0) x 10(-3) min-1] than patients with pneumonia-associated ARDS (lung injury score > or = 2.5, n = 8), and an average pulmonary leak index of 37.5 [(23.4-144.2) x 10(-3) min-1], so that, for all patients, the pulmonary leak index, averaged for both lungs, directly related to the lung injury score (r2 = 0.61, P < 0.01). A normal average pulmonary leak index excluded pneumonia-associated ARDS. Patients with unilateral pneumonia had a greater inter-lung difference (P < 0.01) in the pulmonary leak index between affected and unaffected lung than patients with bilateral pneumonia. The index did not have prognostic significance. 4. The 67Ga-transferrin pulmonary leak index parallels the degree of radiographic, ventilatory and lung mechanical abnormalities of pneumonia and evolving ARDS. The data support the idea that the clinical manifestations of pneumonia culminating in ARDS directly relate to the degree of microvascular injury. Conversely, the pulmonary leak index may be used to monitor the effect of anti-inflammatory drugs in the adjunctive treatment for severe pneumonia aimed at circumventing mechanical ventilation in future studies.