Leptin, a 16-kDa adipocyte-derived protein whose circulating levels reflect energy stores, increases the resting metabolic rate and thermogenesis in rodents. Thyroid hormones also increase the basal metabolic rate, but nothing is known about possible interactions between leptin and thyroid hormone. Activation of β-adrenergic receptors decreases leptin levels in rodents. To test the hypothesis that thyroid hormones, by causing a “functional hyperadrenergic” state, result in decreased leptin concentrations in humans, we studied 22 normal healthy men before and after the administration of T₃ for 1 week to induce moderate hyperthyroidism. Short term thyroid hormone excess does not alter circulating leptin concentrations despite a demonstrated effect on heart rate, systolic blood pressure, cholesterol levels, and metabolic indexes of bone turnover. Elucidation of the apparently separate pathways by which thyroid hormones, β-agonists, and leptin regulate energy expenditure and food intake may have important implications for our understanding of the mechanisms for regulating energy homeostasis in health and disease.