The effect of meal-induced changes in serum free tryptophan (TRP) levels on brain TRP levels was examined in streptozotocin-diabetic rats. Diabetic rats, fasted overnight, were given free access to a non-protein food containing either no fat or large amounts of fat (45% by weight), and were killed 1, 2 or 3 hr thereafter. Ingestion of the high-fat meal produced large increases in both serum non-esterified fatty acid (NEFA; 2-fold) and free TRP levels (2.5-fold), but no increments in cerebral cortical or hypothalamic TRP levels or in the rate of serotonin synthesis in these brain regions. Because the rats were diabetic, serum levels of the other large neutral amino acids (which compete with TRP for transport into brain) did not vary from fasting values in any of the treatment groups. There thus was no uncontrolled variation in the competitive transport of TRP into brain that might have obscured potential effects due to the alterations in serum free TRP levels. The results add further evidence to the notion that TRP transport into the central nervous system is not influenced by the size of the free TRP pool in blood.