Patients requiring prolonged (greater than 24 hours) mechanical ventilation have various conditions that result in respiratory failure. All patients requiring prolonged mechanical ventilation were subdivided into the following six groups: uncomplicated acute lung injury; respiratory failure complicated by multisystem failure; previous lung disease; trauma; other medical causes; and routine postoperative ventilation. During a one-year period, 327 patients required prolonged mechanical ventilation; acute lung injury and chronic obstructive pulmonary disease were the predominant conditions. Sepsis was both the major predisposing factor for and complication of acute lung injury. Mortality for patients with acute lung injury was 40 percent in the uncomplicated group and 81 percent in patients with acute lung injury complicated by multisystem failure. Acute respiratory failure in association with acute renal failure had a mortality of 89 percent. Number of organ systems involved also correlated with mortality. In patients with chronic obstructive pulmonary disease and pneumonitis or retained secretions, mortality was lower (30 percent), but a significant percentage of these patients (43 percent) became ventilator-dependent. Ventilator dependence did not significantly increase mortality during the course of respiratory failure.