In nine obese but otherwise healthy subjects the effect of caloric restriction on the serum concentrations of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), urea, uric acid, creatinine, and bilirubin was studied. Blood was obtained before and 2, 4, and 6 wk after the subjects had changed to a chemically defined diet (31 g amino acids, 44 g carbohydrate, and 1.5 g fat; 300 kcal/day). A decline of body weight to 88% and of serum T3 to 70% of the pretreatment values was observed. Creatinine and bilirubin increased to 115% and 163%, respectively. Uric acid and rT3 showed a transient rise to 148% and 180%, respectively. Serum urea was lowest (72%) from the second until the fourth week. There was a highly significant correlation between serum rT3 and uric acid (r = 0.77, p less than 0.001). The time course of the changes seems to indicate that conversion of T4 into T3 and rT3 is mediated by separate processes.