Abstract The effects of moderate hyperthyroidism on lipid metabolism were investigated in six healthy subjects before and after thyroxine treatment (300 μg/d). T 4-treatment increased basal metabolic rate (+8%) and glucose oxidation (+87%), without affecting lipid oxidation, plasma free fatty acids, glycerol, and β-hydroxybutyrate. During euthyroidism, a hypoinsulinaemic-euglycaemic 150-minute clamp protocol increased energy expenditure (+3%), lipid oxidation (+42%), plasma free fatty acids (+254%), glycerol (+232%), and β-hydroxybutyrate (+343%), but decreased glucose oxidation (−20%). Similar effects were observed after T 4-treatment, but hyperthyroidism induced disproportionate increases in energy expenditure (+7%), plasma glycerol (+310%), and ketone body levels (+436%). We conclude that moderate hyperthyroidism enhances hypoinsulinemia-induced increases in lipolysis, free fatty acid recycling, and ketogenesis without affecting lipid oxidation. Thus basal insulin may camouflage some of thyroid hormone action on lipid metabolism.