In order to determine if reduced serum T3 concentrations contribute to the decrease in resting metabolic rate (RMR) during rapid weight loss, we administered T3 (30 micrograms/d) and T4 (100 micrograms/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 T3 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 T3 and T4 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 T3 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.