1.The percentage of human plasma tryptophan in the free state (ultrafilterable) was positively and significantly correlated with plasma non-esterified fatty acid (NEFA) concentration.2. Results obtained either by adding tryptophan to plasma in vitro or from plasma taken during tryptophan infusion indicate one tryptophan binding site per albumin molecule and an inverse relationship between binding constants and NEFA concentration.3. A single normal subject was atypical as the apparent number of binding sites varied between one and two per albumin molecule (1.54rt0.49 SD, four experiments).4. Spontaneous increases of plasma NEFA during tryptophan infusion were associated with increased free tryptophan. Also addition in uitro of linoleic acid, oleic acid and palmitic acid to plasma caused free tryptophan to increase. 5. The possible significance of NEFA changes on plasma tryptophan binding in various pathological circumstances is discussed.