Death from pulmonary failure in clinical shock is largely due to alterations in pulmonary venous admixture with ventilation-perfusion (V/Q) abnormalities which are related to very early increases in pulmonary vascular resistance; the latter is an important early predictor of survival.Sequential hemodynamic, oxygen transport and pulmonary venous admixture measurements were performed in experimental animals as well as in shock patients remote from therapy. In surviving patients, the early physiologic response consisted of hypotension, increased PVR, normal arterial pH, and normal central blood volume. There was an increased cardiac output with normovolemia and usually decreased cardiac output in the presence of hypovolemia. During the early period of shock, the nonsurvivors had lower cardiac output, higher central blood volume, higher PVR, greater acidosis, and lower oxygen consumption.Increased PVR occurred early, often before development of maximal hypotension and low cardiac output in both clinical and experimental conditions. The magnitude of the PVR increase was roughly related to the extent of the trauma and hemorrhage; the increase was significantly greater in nonsurvivors. The increased PVR was associated with acidosis during hypovolemia, increased central blood volume after volume deficits were restored, and with the subsequent appearance of pulmonary shunting.These data indicate that trauma, hemorrhage and other forms of stress produce pulmonary vasoconstriction from neural influences; initially at least, this is a compensatory mechanism which tends to redistribute blood flow upward. However, the increased PVR may be exaggerated by metabolic, hormonal, and rheologic factors. The persistence of a high PVR leads to the backup of blood behind the lesser circulation and uneven blood flow in the microcirculation. Thus, ventilation-perfusion abnormalities are produced by maldistributions of regional or zonal pulmonary blood flow as well as maldistributions of flow at the microcirculatory level. Therapy is directed toward the reduction of PVR by correction of acidosis, the use of plasma expanders and steroids, and the avoidance of vasopressors and saline.