This study investigates the function of pancreatic alpha cells in healthy and diabetic subjects using a highly specific glucagon radioimmunoassay. In healthy nondiabetic subjects, mean fasting plasma glucagon levels averaged 108 μg/ml, with a significant rise to 331 μg/ml during arginine infusion. Diabetic subjects, including both juvenile-type and adult-type diabetics, exhibited similar fasting glucagon levels (110-114 μg/ml) but showed a marked hyperresponsiveness to arginine infusion, with mean glucagon levels rising to 458 μg/ml and 452 μg/ml, respectively. The hyperresponsiveness to arginine was not influenced by the duration of diabetes, body weight, or type of diabetic treatment. The study suggests that alpha cell function is appropriately increased in diabetes and may play a significant role in the pathophysiology of the diabetic syndrome.This study investigates the function of pancreatic alpha cells in healthy and diabetic subjects using a highly specific glucagon radioimmunoassay. In healthy nondiabetic subjects, mean fasting plasma glucagon levels averaged 108 μg/ml, with a significant rise to 331 μg/ml during arginine infusion. Diabetic subjects, including both juvenile-type and adult-type diabetics, exhibited similar fasting glucagon levels (110-114 μg/ml) but showed a marked hyperresponsiveness to arginine infusion, with mean glucagon levels rising to 458 μg/ml and 452 μg/ml, respectively. The hyperresponsiveness to arginine was not influenced by the duration of diabetes, body weight, or type of diabetic treatment. The study suggests that alpha cell function is appropriately increased in diabetes and may play a significant role in the pathophysiology of the diabetic syndrome.