The acute respiratory distress syndrome may complicate both pulmonary and extrapulmonary conditions. There is a growing belief that the predisposition to, and clinical course of, the syndrome may be influenced by the extent to which the lung is directly involved in the precipitating pathologic changes. Several studies have highlighted differences in morphology and respiratory physiology between the two subgroups in the early stages of acute respiratory distress syndrome. Further, preliminary reports have suggested that the effects of therapeutic interventions such as alterations in positive end-expiratory pressure, prone ventilation, and the use of inhaled vasoactive agents may differ between pulmonary and extrapulmonary acute respiratory distress syndrome. There are, however, inconsistencies between various studies addressing these issues, which may relate in part to differences in etiologic case mix. There are also practical difficulties in assigning certain cases to one of these two groups. Finally, there are as yet no outcome data to support any modification of clinical management on the basis of this distinction.