Changes in oxygenation after oleic acid (OA)-induced acute lung injury were correlated to changes in extravascular lung water (EVLW) and hemodynamics in 19 mongrel dogs. Three patterns seemed apparent. In group 1 (seven dogs) EVLW increased by 88% from control values but Pa(O2) fell only 15%. The change in Pa(O2) in this group was related directly to the change in mixed venous O2 tension (P(V̄O2)) after the OA-induced fall in cardiac output. In group 2 (eight dogs), EVLW rose by 120% and PaO2) fell 53%, 90 min after OA administration. In this group, there was a subsequent spontaneous improvement of Pa(O2) to 75% of control values, without any measured change in EVLW. In group 3 (four dogs), the fall in Pa(O2) was comparable to that of group 2, but the increase in EVLW was greater (148%) and there was no spontaneous improvement in oxygenation. Cardiac index fell in all three groups. A small but significant increase in P(V̄O2) partially explains the improvement in oxygenation in group 2. We conclude that changes in oxygenation are a poor index of injury during this model of acute lung injury and that the course of oxygenation is directly related to measured changes in EVLW and hemodynamics.