Because transthyretin (TTR) is a tryptophan-rich molecule and a sensitive nutritional marker, tryptophan deficiency might markedly influence the circulating level of TTR. The effect of severe tryptophan (Trp) deficiency on serum TTR, as well as on albumin and transferrin levels, was studied in growing rats for 8 d. The animals were then refed a control diet for 12 d. The Trp-deficient and control diets contained 0.008 and 0.34% Trp, respectively. A loss of body weight and a dramatic reduction in food intake were observed in the Trp-deficient rats. Although serum total Trp concentration was significantly less in these rats than in pair-fed controls, serum TTR declined to the same extent in both groups compared to control rats fed ad libitum. Albumin concentrations were not altered, but transferrin levels declined slightly in the Trp-deficient rats compared to both the pair-fed group and the controls fed ad libitum. Refeeding the control diet to Trp-deficient rats restored total and free Trp concentrations, as well as TTR and transferrin levels, but body weight and food intake remained lower than in the control group. To examine the effect of moderate Trp restriction, rats were fed for 2 wk a diet whose Trp content was 50% less than that of the control diet. Although total and free Trp concentrations were significantly lower in the rats fed the Trp-deficient diet than in the control group, body weight, food intake and TTR levels were similar in both groups. The results suggest that acute and severe Trp deficiency per se does not modify TTR and albumin levels.