Previous work with human subjects has demonstrated a relationship between the amount of carrier added to a tracer dose of DL-tryptophan-2-C14 and the percent of the C14 expired as CO?. As the level of carrier added to a dose of labeled tryptophan was increased from zero to 2 g, the percent of CI4 expired as C 0 2 in 24 hours increased from 4.5 to 25% ( 1 ) . The data suggested that given quantities of tryptophan were converted into proteins and enzymes, but that the excess was metabolized to CO? probably via the glutarate pathway(2,3). In view of this and several reports of in vitro and in vivo effects of tryptophan metabolites on enzymes related to this pathway, as well as other systems (4,5,6), and because of the increasing evidence that some tryptophan metabolites are carcinogenic (7,8), it was considered of intereslt to investigate the in vivo metabolism of DL-tryp-t0phan-7a-C~~ as affected by loading doses of L-tryptophan, DL-kynurenine, 3-hydroxyanthranilic acid and quinolinic acid. The loading doses used were equivalenlt, on a molar basis, to a 2 g load of tryptophan in a 70 kg man, a load which has been used extensively(9), and which has been recommended as a standard test dose for studies of tryptophan metabolism in humans.Experimental. An aqueous solution of DLtryptophan-7a-C1* (5.76 pc/mg) containing 1.064 mg per ml was injected intraperitoneally into pairs of rats (400-500 g) a t a level of 0.67 ml per kg of body weight. The unlabeled tryptophan, DL-kynurenine sulfate, 3-hydroxyanthranilic acid and quinolir$ic acid were also injected intraperitoneally a t a dosage level of 0.14 mMole per kg of body weight, which would represent on an equimolar basis a 2.0 g dose of L-tryptophan in a 70 kg man. The respiratory C 0 2 was collected for 12 hours and the urine for two 12hour periods. The urine samples were assayed for quinolinic acid (QA) ( 10) and nicotinic acid ( 11). By use of carrier techniques these labeled metabolites were isolated frolm only the first 12-hour urines( 12) , since the major portion of the excreted radioactivity and metabolite were in this fraction of urine. The urines were not assayed for kynurenine, oaminohippuric acid, xanthurenic acid, N1methylnicotinamide, or N-methyl-2-pyridone-5-carboxamide because of limited amounts of sample, but the carbon-14 labeled components of these metabolites were isolated by carrier techniques .For the isolation of o-aminohippuric acid, N * -methyl n ico t i namide, xan t hurenic acid, and N-methyl-2-pyridone-5-carboxamide, the column separation described by McCoy and Chung( 13) was used. Tot 30 percent of the rat urine was added 1.0 mg of the above compounds to allow spectrophotometric k y n ur enine,