The precise roles of hypoxia in the initiation and progression of kidney disease remain unresolved. A major technical limitation has been the absence of methods allowing long-term measurement of kidney tissue oxygen tension (Po(2)) in unrestrained animals. We developed a telemetric method for the measurement of kidney tissue Po(2) in unrestrained rats, using carbon paste electrodes (CPEs). After acute implantation in anesthetized rats, tissue Po(2) measured by CPE-telemetry in the inner cortex and medulla was in close agreement with that provided by the gold standard Clark electrode. The CPE-telemetry system could detect small changes in renal tissue Po(2) evoked by mild hypoxemia. In unanesthetized rats, CPE-telemetry provided stable measurements of medullary tissue Po(2) over days 5-19 after implantation. It also provided reproducible responses to systemic hypoxia and hyperoxia over this time period. There was little evidence of fibrosis or scarring after 3 wk of electrode implantation. However, because medullary Po(2) measured by CPE-telemetry was greater than that documented from previous studies in anesthetized animals, this method is presently best suited for monitoring relative changes rather than absolute values. Nevertheless, this new technology provides, for the first time, the opportunity to examine the temporal relationships between tissue hypoxia and the progression of renal disease.