To investigate the antihyperglycaemic effect of metformin (dimethylbiguanide), insulin binding and glucose metabolism were examined in soleus muscles isolated from streptozotocin diabetic mice. Treatment with metformin (250 mg/kg/day orally for 3 weeks) reduced by 39% the severity of streptozotocin-induced hyperglycaemia. Soleus muscles of metformin treated mice showed a 41% increase in total insulin receptor number, and a 20% increase in 3-0-methylglucose uptake at both submaximally and maximally stimulating insulin concentrations. Oxidation of U-14C-glucose to 14CO2 and the formation of 14C-glycogen were increased by 25% and 30% respectively at maximally stimulating insulin concentrations, but not at submaximally stimulating concentrations. Lactate formation was not significantly altered. Maximum activity of hexokinase (EC 184.108.40.206) was increased by 35%, and this effect was independent of insulin. The results suggest that the antihyperglycaemic effect of metformin in streptozotocin diabetic mice is related in part to an increase in insulin-mediated glucose uptake and oxidative metabolism in skeletal muscle.