OBJECTIVE The endothelial cell produces many bioactive compounds that are presumed to play important roles in the pathogenesis of the adult respiratory distress syndrome (ARDS). We postulated that individuals with sepsis and trauma-two at-risk diagnoses for the development of ARDS--might demonstrate differences in the degree of endothelial cell activity. METHODS Prospective cohort study. METHODS Intensive care unit patients in a tertiary, university-affiliated, city hospital. METHODS Fifty-five intensive care unit patients (19 with sepsis and 36 trauma patients). METHODS Plasma measurements of three endothelial cell products--von Willebrand factor antigen, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble E-selectin-were performed within 8 hrs of patients meeting our inclusion criteria, and at the clinical onset of ARDS. RESULTS Twenty-six percent of the septic patients and 25% of the trauma patients developed ARDS. The median (and 25% to 75% quartiles) concentrations of all three mediators measured in the sepsis patients (von Willebrand factor antigen 399% [375% to 452%], ICAM-1 573 ng/mL [470 to 980], and soluble E-selectin 180 ng/mL [81 to 340]) were significantly higher (p < .001 for each individual analysis) than in the trauma patients (von Willebrand factor antigen 256% [217% to 310%], ICAM-1 148 ng/mL [113 to 210], and soluble E-selectin 42 ng/mL [31 to 65 ng/ mL]). In addition, neither the ICAM-1 nor soluble E-selectin concentrations measured in the trauma patients were different (p = .17 and p = .24, respectively) from normal controls. In those patients who developed ARDS, the differences in the concentrations of all three endothelial cell mediators between the sepsis and trauma patients persisted (p = .008 for von Willebrand factor antigen, p = .003 for ICAM-1, and p = .003 for E-selectin). CONCLUSIONS These findings suggest that differences in endothelial cell activity exist between sepsis and trauma patients who are at risk for the development of ARDS.