The net renal metabolism of amino acids and ammonia in the post absorptive state was evaluated in subjects with normal renal function and in patients with chronic renal insufficiency by measuring renal uptake and release, and urinary excretion of free amino acids and ammonia. In normal subjects the kidney extracts glutamine, proline, citrulline, and phenylalanine and releases serine, arginine, taurine, threonine, tyrosine, ornithine, lysine, and perhaps alanine. The renal uptake of amino acids from arterial blood occurs by way of plasma only, whereas approximately a half of amino acid release takes place by way of blood cells. Glycine is taken up from arterial plasma, while similar amounts of this amino acid are released by way of blood cells. In the same subjects total renal ammonia production can be largely accounted for by glutamine extracted. In patients with chronic renal insufficiency (a) the renal uptake of phenylalanine and the release of taurine and ornithine disappear; (b) the uptake of glutamine and proline, and the release of serine and threonine are reduced by 80--90%; (c) the uptake of citrulline and the release of alanine, arginine, tyrosine, and lysine are reduced by 60--70%; (d) no exchange of glycine is detectable either by way of plasma or by way of blood cells; (e) exchange of any other amino acid via blood cells disappears, and (f) total renal ammonia production is reduced and not more than 35% of such production can be accounted for by glutamine extracted, so that alternative precursors must be used. A 140% excess of nitrogen release found in the same patients suggests an intrarenal protein and peptide breakdown, which eventually provides free amino acids for ammonia production.