Hyperthyroidism is considered to be an insulin-resistant state, but a quantitative evaluation of some action of insulin is still lacking. We performed euglycaemic clamp at about 350 and 7000 pmol l-1 plasma insulin concentration in combination with the 3H-glucose infusion in 12 patients with Graves' disease and in 12 matched controls. Fasting plasma insulin (126 +/- 6.5 vs. 77.5 +/- 5.7 pmol l-1; P less than 0.001), C-peptide (502 +/- 36 vs. 363 +/- 41 pmol l-1; P less than 0.001) and glucagon (47 +/- 3.3 vs. 33.3 +/- 3 pmol l-1; P less than 0.01) were significantly higher in hyperthyroids than in euthyroids. Basal hepatic glucose production was significantly higher in hyperthyroids than in euthyroids (18.3 +/- 1.4 vs. 9.2 +/- 0.5 mumol l-1; P less than 0.0001), and its suppression during physiological hyperinsulinaemia was only 50% in hyperthyroids. Glucose utilization and suppression of lipolysis were normally stimulated by insulin. All parameters altered during hyperthyroidism were normalized during methimazole-induced euthyroidism. We conclude that insulin resistance involves mainly glucose rather than lipid and is selective at the hepatic level.