Pulmonary and systemic vascular responses to vasoactive substances, injected distal to a pulmonary artery balloon, were studied in dogs. Extract of lung homogenate, serotonin, or histamine injected in the pulmonary artery distal to an obstruction caused pulmonary hypertension. If the animal was pretreated with proteinase inhibitor, the pulmonary vascular reactivity to extract of lung homogenate and serotonin was obviated. This was not true of the reaction due to histamine. These findings suggest that stasis of vasoactive substances may be an important consideration in the concept of a humoral component in pulmonary embolism.