The characteristics and outcome of acute respiratory distress syndrome (ARDS) may have changed with time. Some studies have reported that mortality is more commonly related to the development of sepsis/multiple organ failure (MOF), and others that it is related to the severity of acute respiratory failure (ARF). The present study evaluates the relative importance of the two phenomena in a large series of patients. The clinical and biological data of all patients who developed ARDS during a 26 month period (January 1993 until February 1995) in our intensive care unit (ICU) were reviewed retrospectively. A total of 129 patients developed ARDS during the study period, representing an incidence of 2.4% of all ICU admissions. The mortality rate was 52%. The primary cause of death was sepsis/MOF (49%), followed by respiratory failure (16%), cardiac failure or arrhythmias (15%), neurological failure (10%), and other causes (8%). The mortality rate was related to age and degree of organ failure. MOF was not always a cause of late death, since half the deaths occurred within 5 days after admission. In addition, mortality was higher in septic than in nonseptic patients, and lower in trauma and surgical than in medical patients. We conclude that sepsis/multiple organ failure is still the most common cause of death in acute respiratory distress syndrome. Improvements in outcome of acute respiratory distress syndrome may depend more on treatment of sepsis and multiple organ failure than on oxygenation measures.