The effect of sustained hyperglucagonaemia on blood glucose concentrations and on insulin requirements was evaluated in 6 fasting insulin dependent diabetic subjects whose blood glucose concentrations were being controlled with a closed loop insulin infusion system. Subjects were iv infused initially with either saline or glucagon and subsequently with the other infusate. All determinations were performed following the period during which transient increases in glucagon stimulated glucose production have been reported to occur. Plasma glucagon concentrations were significantly higher during the glucagon study period (491 +/- 65 vs 70 +/- 13 pg/ml +/- SD, P less than 0.001) as were blood glucose concentrations (104 +/- 2 vs 84 +/- 7 mg/ml +/- SD, P less than 0.001) and insulin requirements (3.5 to 36.5 vs 0 to 2.3 mU/kg/h, P less than 0.05). Sustained hyperglucagonaemia continues to have an effect on glucose homeostasis for at least 2 h following the initiation of a continuous infusion.