BACKGROUND: In hyperthyroidism, although hepatic insulin resistance is well established, information on the effects of insulin on glucose uptake in skeletal muscle is variable. METHODS: To investigate this, a meal was given to nine hyperthyroid (HR) and seven euthyroid (EU) subjects. Blood was withdrawn for 360 min from a forearm deep vein and the radial artery for measurements of insulin and glucose. Forearm blood flow (BF) was measured with strain-gauge plethysmography. Glucose flux was calculated as arteriovenous difference multiplied by BF and fractional glucose extraction as arteriovenous difference divided by arterial glucose concentrations. RESULTS: Both groups displayed comparable postprandial glucose levels, with the HR having higher insulin levels than the EU. In the forearm of HR vs. EU: 1) glucose flux was similar [area under the curve (AUC)(0-360) 673 +/- 143 vs. 826 +/- 157 micromol per 100 ml tissue]; 2) BF was increased (AUC(0-360) 3076 +/- 338 vs. 1745 +/- 145 ml per 100 ml tissue, P = 0.005); and 3) fractional glucose extraction was decreased (AUC(0-360) 14.5 +/- 3 vs. 32 +/- 5%min, P = 0.03). CONCLUSIONS: These results suggest that, in hyperthyroidism, insulin-stimulated glucose uptake in muscle is impaired; this defect is corrected, at least in part, by the increases in BF.