To investigate the role of -adrenergic mechanisms in the counterregulatory response of the liver and kidney to hypoglycemia, we studied 10 dogs before and after a 2-h constant infusion of insulin (4 mU · kg¹ · min¹) either without (n = 4) or with (8 µg/min, n = 6) propranolol and variable dextrose to maintain hypoglycemia, 7 days after surgical placement of sampling catheters in left renal and hepatic veins and femoral artery. Systemic glucose appearance (R_a) and endogenous (EGP), hepatic (HGP), and renal (RGP) glucose production were measured by a combination of arteriovenous difference and peripheral infusion of [6-³H]glucose, renal blood flow with a flow probe, and hepatic plasma flow by indocyanine green clearance. Without -adrenergic blockade, arterial glucose decreased from 5.12 ± 0.02 to 2.53 ± 0.07 mmol/l, glucose R_a increased from 17.8 ± 0.7 to 30.5 ± 2.5 (P < 0.01) when EGP was 22.2 ± 0.5, HGP from 13.5 ± 1.1 to 19.3 ± 1.3, and RGP from 2.4 ± 1.0 to 8.6 ± 0.9 µmol · kg¹ · min¹ (all P < 0.05). When propranolol was infused, glucose decreased from 5.97 ± 0.02 to 2.71 ± 0.03 mmol/l, glucose R_a increased from 16.3 ± 1.0 to 25.1 ± 1.6 when EGP was 9.9 ± 0.4, HGP decreased from 14.4 ± 0.7 to 10.4 ± 0.6, and RGP decreased from 3.8 ± 1.3 to 1.1 ± 0.8 µmol · kg¹ · min¹ (all P < 0.05). Our data indicate that -adrenergic blockade impairs glucose recovery during sustained hypoglycemia, in part, by preventing the simultaneous compensatory increase in HGP and RGP.