Isolated perfused rat lungs removed more than 35% of 3H-cortisone (1 × 10-9M) from the perfusate during one passage through the pulmonary circulation. The cortisone in the lung was then rapidly converted to cortisol, which was returned to the perfusate. The tritiated steroid taken up was so rapidly washed from the lung, that only 10% remained after a 12 minute perfusion with steroid-free medium. In recirculating experiments, nearly 60% conversion to cortisol occurred over 32 cycles; in addition, there was a slow increase in the percentage of polar compounds in the medium. Similarly, the perfused hindlimbs preparation from the rat converted cortisone to cortisol and returned the cortisol to the perfusate. In contrast, guinea pig isolated perfused lungs had negligible effect on cortisone. Rat lungs demonstrated only a limited ability to convert 3H-cortisol to cortisone. The results suggest that the lungs may play an important role in maintaining cortisone/cortisol levels in the plasma.