The turnover rate of glucose was measured in dogs with indwelling arterial and venous catheters, according to the primed constant rate infusion techniques, using 2-3H-glucose as tracer. The effects of adrenalin (A), noradrenalin (NA), and dibutyryl-cAMP (DBcAMP) infusions were tested on normal dogs and on dogs treated for 3 days with methylprednisolone (MP, 3–3.5 mg/kg day). MP potentiated the hyperglycemic effect of A (0.5 μg/kg min) six- to sevenfold, and the increase of hepatic glucose output (Ra) 11-fold. In addition, the free fatty acid (FFA) increasing and lactacidemic effects of A were significantly potentiated by MP. A prevented the rise of immunoreactive insulin even though plasma glucose reached values of 400–450 mg%. The metabolic clearance rate was significantly decreased by A. NA (0.5 μg/kg min) had no hyperglycemic effect in the controls, but it increased the blood sugar by 120 mg% in the treated group. This was caused by a more than twofold increase in the hepatic glucose output. MP treatment did not alter the NA induced rise of FFA and no effect was seen on plasma lactate levels. NA caused a transient rise of insulin in the controls and a greater and more sustained one in treated dogs. Following MP treatment, DBcAMP (0.1 or 0.2 mg/kg min) also caused a much greater hepatic glucose output and hyperglycemia than what had been obtained on the same animals prior to treatment. DBcAMP increased plasma insulin and decreased FFA. It is concluded that the cyclic-AMP sensitivity of hepatic enzyme systems involved in glucose output was greatly increased by MP treatment.