SUMMARYThe relationship between the changes in serum thyroid hormone levels and nitrogen economy during caloric deprivation were investigated in ten obese men during a 40 d, 400 kcal protein‐supplemented weight‐reducing diet. This regimen induced increases in the serum levels of total T4, free T4 and total rT3, and decreases of total T3, while serum TSH remained unchanged. There were progressive decreases in total body weight and urinary losses of total nitrogen and 3‐methylhistidine, with the early negative nitrogen balance gradually returning towards basal values during the 40 days. Subjects with the largest weight loss had the most increase in the serum levels of total T4 and free T4 index and the greatest decrease in T3. The magnitude of the increase of the nitrogen balance from its nadir was correlated with the extent of the reduction of T3 and increase of T3 uptake ratio and free T4 levels. The decrease in the urinary excretion of 3‐methylhistidine correlated with the increase in free T4 and rT3 levels. Nadir serum transferrin values were directly related to peak rT3 values, and the lowest albumin concentrations occurred in subjects with the highest total T4 and free T4 index values. Further, the maximum changes in the serum thyroid hormone levels preceded those of the nutritional parameters. These relationships suggest that: (1) increases in serum rT3 and free T4 and reductions in T3 concentrations during protein supplemented weight reduction may facilitate conservation of visceral protein and reduce muscle protein turnover; and (2) the variation in the magnitude of these changes may account for the heterogeneity of nitrogen