It has been suggested that regional oxygen metabolism may be measured quantitatively by analysis of the steady-state distribution of O-15 (T1/2 = 122 sec). For this analysis we have developed a compartmental model that incorporates corrections due to clearance and recirculation of water of metabolism. The oxygen utilization rate is simply proportional to the local O-15 activity if water of metabolism is not recirculated from other tissues and is not lost to the circulation for a time long compared with the half-life of O-15. We evaluated the magnitude of biological metabolic water loss and uptake in the steady state. Our analysis indicates that the magnitude of these effects for rapidly exchanging tissues (such as cerebral gray and white matter), may preclude a simple, noninvasive, and quantitative determination of regional oxygen metabolism. Slowly exchanging compartments, however (such as skeletal muscle and perhaps some tumors), appear amenable to correction for clearance and recirculation effects with sufficient accuracy to make determinations of regional oxygen metabolism feasible.