Guanidinosuccinic acid (GSA), a nitrogenous metabolite isolated in excess from serum and urine, in uremia is a prime candidate for the role of a uremic toxin. It is excreted in small quantities by normal individuals at a relatively constant rate which increases after high protein intake. Twenty-four hour urinary excretion increases in animals following instillation of materials from which arginine is synthesized, is unchanged following those which are end products of arginine breakdown and is depressed in those conditions in humans which involve congenital absence of arginine synthetic enzymes. Guanidinoacetic acid, which suppresses arginine breakdown by a mechanism involving enzyme retroinhibition, is poorly excreted by the failing kidney and is, consequently, increased in uremic plasma. This is proposed as a mechanism for the genesis of GSA and suggests a method of detoxification.