On the basis of observations in surgically created remnant kidneys of rat and dog, a novel hypothesis for progressive injury in the setting of reduced renal mass has been put forth. Both rat and dog remnant kidneys exhibit significant hypertrophy that is accompanied by an increased rate of oxygen consumption (QO2) per remaining nephron but not per gram of tissue. This putative "hypermetabolism" is seen in the face of progressive scarring of the tubulointerstitial compartment of the remnant kidney, and interventions that reduce QO2 in these models have been associated with reduced tissue injury in previous studies. The proposed pathway by which an increase in QO2 leads to cellular damage is via the production of oxygen-reactive species or free radicals. In this article, the available data upon which this "hypermetabolism" hypothesis is based are reviewed and the constructs within which these data have been analyzed are examined. From these considerations, a set of questions not yet answered that may serve to direct more fruitful query into this intriguing problem