Regional pulmonary blood flow was measured by external counting of intravenously injected (133)Xe during 20 min of breathing 14.2% oxygen and during 20 min of recovery from hypoxia. 16 normal human volunteers were studied, nine sitting and seven supine. During hypoxia there was a slight but significant increase in relative perfusion of the upper portions of the lungs in both the sitting and supine subjects. During recovery from hypoxia, blood flow distribution differed significantly from the control. The erect subjects showed increased relative perfusion of the lung bases and the supine subjects showed increased relative perfusion of the upper zones. Comparison of the distribution of inhaled and intravenously injected isotope showed that in the sitting subjects the altered distribution during hypoxia tended to make alveolar oxygen tension more uniform. In the supine subjects, however, the shift in blood flow increased the perfusion of the regions with the lowest ventilation/perfusion, tending to accentuate uneven alveolar oxygen tension. Therefore it does not seem that the altered blood flow distribution during hypoxia was due to selective vasoconstriction in the regions of lowest alveolar oxygen tension, but rather that vasoconstriction was greatest in the lower lung zones because the vessels there are more responsive to hypoxia. During mild acute hypoxia, vasoconstrictor tone does not seem to effectively match ventilation and perfusion. The altered distribution of pulmonary blood flow during recovery from hypoxia suggests the occurrence of posthypoxic vasodilation. Failure to consider this possibility may lead to erroneous interpretation of pulmonary hemodynamic measurements made after the inspired oxygen concentration has been changed.