The first naturally occurring amino acid to be described was asparagine, which Vauquelin and Robiquet detected in asparagus juice in 1806 (from Ref. 354); the second amino acid, cystine, was discovered in the urine of a patient suffering from urolithiasis by Wollaston (641) in 1810. He called it “cystic oxide,” not recognizing its chemical structure at that time. Today we know that this early detection of a urinary amino acid was only possible because the kidney of this patient failed to reabsorb cystine properly. It took another 90 years until Pfaundler (416) detected the small amounts of amino acids in normal urine.(For more historical facts in this field see Refs. 354,601,648.) If we add up the concentrations of all free plasma amino acids and multiply the resulting 2.5 mM by the glomerular filtration rate (GFR), a daily load of-450 mmol of amino acids enters the lumen of the tubules at the glomeruli in a human. Already in 1917 Cushny (131) stated in his famous textbook that powerful resorption mechanisms located along the tubular walls ensure that normally almost all the filtered load is removed from the tubular urine and return. ed to the blood. The locali zation along the tubule, the kinetics and specificity, the driving forces, and the bi. ochemical. nature of these reabsorptive mechanisms are the main topics of this review. Renal handling of amino acids includes more than this process, however. Amino acids/not only enter the tubular cells from the lumen but, as in all other cells, also enter from the (peritubular) blood (169, 1’71,174). This flux opposes the cellular exit of amino acids of luminal origin. With the assumption that amino acids taken up on the two sides of the tubular cell enter the same pool, transepithelial transport becomes more complex than originally expected. The situation is even more complicated if we also consider tubular amino acid metabolism. Besides being involved in the usual formation and hydrolysis of domestic cell proteins, a topic not treated in this review, renal amino acid formation and breakdow n are also important for metabolism in the whole body. Renal glutamine breakdown, for instance, plays a key role in acid-base balance by yielding NH4+ for urinary excretion, and renal conversion of citrulline to arginine is the most important source of this dibasic amino acid in the whole body (160,406,634). Finally, the kidney is an important organ for protein and peptide degradation. Smaller peptides, including angiotensin and glutathione, filtered at the glomeruli and possibly secreted (glutathione 1) ou. t of the tubular ccl ls, are hydrolyzed within the tubular