We have measured the effects of normobaric hyperoxia on arterial and mixed venous gas tensions, cardiac output, heart rate, right atrial, pulmonary, and aortic pressures in 12 conscious chronically instrumented sheep. Regional blood flow to brain, heart, kidney, intestines, and respiratory muscles was assessed in five sheep by injecting 15 μm microspheres labeled with γ-emitting isotopes. Survival time ranged from 60 to 120 h (mean = 80 h). All variables except arterial O2 partial pressure (Pa(O2)) and mixed venous O2 partial pressure remained at base-line level during the first 40 h of exposure, after which Pa(O2) decreased gradually but remained above 200 Torr at death. After this there was a progressive uncompensated respiratory acidosis with terminal arterial CO2 partial pressure values exceeding 90 Torr. There was a considerable rise in the brain blood flow, whereas flow to the other organs either remained unchanged or increased in proportion to cardiac output. Our experiments also showed that systemic hyperoxic vasoconstriction did not occur, and any local changes were not of sufficient magnitude to affect perfusion.