Abstract In order to determine if reduced serum T 3 concentrations contribute to the decrease in resting metabolic rate (RMR) during rapid weight loss, we administered T 3 (30 μg/d) and T 4 (100 μg/d) to obese subjects receiving a very low energy diet to reverse a decrease in serum thyroid hormone concentrations. During the first two weeks of weight loss, before thyroid hormone replacement, the mean RMR of five obese subjects declined to 86% of the baseline level as the mean serum T 3 concentration decreased to 72% of the baseline level. Thyroid hormone replacement for one week, while the low energy diet continued, increased the mean RMR to 94% of the baseline level while increasing mean serum T 3 and T 4 concentrations to approximately 130% of the baseline level. A second week of thyroid treatment caused no further change in RMR. These data suggest that reduced serum T 3 concentrations contribute to the decrease in RMR during rapid weight loss. However, the regimen of thyroid hormone replacement employed did not completely restore a normal RMR in obese subjects on a very low energy diet, in spite of elevating serum thyroid hormone concentrations slightly above weight-maintenance levels.