Using a healthy canine model, we evaluated the influence of renal physiological activity on the stability, intrarenal distribution, and clearance of aztreonam and compared the results with the concentrations of aztreonam that can be achieved in the scarred devitalized renal tissues of patients with end-stage kidney disease. Renal physiological activity significantly modulates the intrarenal distribution of aztreonam. During the production of maximally acid-concentrated urine, urinary aztreonam levels, clearance rates, and inner zone renal tissue concentrations are increased. Aztreonam concentrations in the parenchyma of severely diseased kidneys are significantly reduced in comparison with healthy tissues; nonetheless, the values are similar to concurrent serum drug levels, a result suggesting that treatment may provide adequate coverage for aztreonam-susceptible organisms.