Changes in carbohydrate metabolism were observed in a diabetic, hypertensive patient managed with Clonidine. After a slight increase in the Clonidine dose, his blood sugar control deteriorated. However, when the Clonidine was withdrawn, the glucose intolerance subsided. Because Clonidine preferentially binds α2-subtype receptors, we investigated animal pancreatic tissue by radioligand binding technique and found it to contain α-adrenergic receptors predominantly of the α2-subtype. In consideration of the response from withdrawal of Clonidine and the results of our radioligand studies, we concluded the glucose intolerance seen in this patient was most likely due to the specific action of Clonidine on α2-pancreatic receptors.