1. The effects of pent-4-enoic acid, an inhibitor of fatty acid oxidation, were studied in dogs undergoing water diuresis and acetazolamide diuresis. Free water excretion and distal solute delivery were increased when infusion of pent-4-enoic acid was superimposed on an increasing mannitol diuresis.
2. Bicarbonate excretion increased significantly when infusion of pent-4-enoic acid was superimposed on maximum acetazolamide diuresis.
3. Phosphate excretion exceeded 90% of filtered load when pent-4-enoic acid was administered under stable free water conditions and increased significantly when pent-4-enoic acid was superimposed on stable acetazolamide diuresis.
4. The results are interpreted as indicating inhibition of proximal tubular reabsorption by pent-4-enoic acid, emphasizing the importance of fatty acids as a major fuel for proximal tubular metabolism.