Abstract Metabolic studies were performed in several patients to determine the effect of a loading dose (1 or 2 Gm.) of L-tryptophan on the metabolism of a tracer dose of (17 to 78 mg.) of DL-tryptophan-2-C 14 . In two patients the per cent of an oral tracer dose of DL-tryptophan -2-C 14 expired as CO 2 was 4.52 and 7.33. These values increased to 24.5 and 22.7 per cent when a 2.0 Gm. load of L-tryptophan was given at the same time. The loading dose did not change total urinary radioactivity appreciably but did increase two-to fourfold the radioactivity in kynurenine and combined kynurenic and xanthurenic acids. Administration of the tracer dose intravenously rather than orally caused an earlier excretion of C 14 O 2 but increased only slightly the total per cent of dose appearing in CO 2 . After an oral dose of labeled tryptophan the activity in serum rose within 1 hour and then remained almost constant for 31 hours, at which time about 6.8 per cent of the activity remained in the serum; after 25 weeks about 0.7 per cent of the dose was present in the serum. A possible explanation of the effects seen with the loading doses of L-tryptophan is that the load of tryptophan saturates certain pathways allowing more of the labeled tryptophan to enter the kynurenine-CO 2 pathway via tryptophan pyrrolase, an enzyme known to adapt to tryptophan administration in other species.