To determine the consistency of the pulmonary vasoconstrictor response to hypoxia, dogs were anesthetized, intubated, and ventilated alternately with air and 10% oxygen. Catheters were placed in the pulmonary artery for measurement of pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, and cardiac output and in the femoral artery for monitoring systemic blood pressure and arterial blood gases. Arterial PCO2 and pH were kept at steady levels throughout by ventilating the dogs with a respirator so that only the isolated effect of hypoxia on the pulmonary vasculature was studied. It was found that there was a progressive rise in the PAP with repeated exposure to the same hypoxic stimulus. In 12 dogs, the mean increase in the PAP was 28% above the base line on the 1st hypoxic exposure, rising to 99% by the 10th exposure over the course of 5 h. It was concluded that interpretation of action of agents blocking or enhancing the hypoxic response must take into account this inherent potentiation of the response on repeated exposure to hypoxia.