Chemotaxis and lysosomal enzyme release in peripheral blood neutrophils taken from patients before, during, and after recovery from the adult respiratory distress syndrome (ARDS) were studied. This allowed for correlation of cellular function with changes in a patient's clinical status. It was found that neutrophils from 8 of 9 patients with the fully developed syndrome exhibited a profound depression of chemotaxis (63% depressed, P = 0.0001) and a fourfold elevation of basal lysosomal enzyme release relative to neutrophils from healthy controls (P = 0.0001). These findings of depression of chemotaxis and enhanced basal enzyme release were also detected in neutrophils taken from 7 of 11 patients in whom clinical risk factors (eg, sepsis, pneumonia) for the syndrome had developed. Following resolution of the adult respiratory distress syndrome, the above changes in neutrophil function resolved in the four patients studied during convalescence. Healthy neutrophils exposed to plasma samples (untreated or zymosan-activated) from control subjects and patients with ARDS could not be distinguished with respect to chemotaxis and enzyme secretion. It is concluded that patients in whom ARDS develops show profound but reversible changes in peripheral neutrophil activity which can be measured following the development of a clinical predisposition for the syndrome. Further, the presence of a humoral substance capable of promoting chemotaxis or enzyme secretion from healthy neutrophils in the untreated plasma of patients suffering from ARDS was not demonstrated. This suggests that alteration of neutrophil activity measured in patients with the fully developed syndrome may be cellular in origin.