The mechanism of hyperglycemia produced by L-dopa was studied in normal trained dogs with 3-3H-glucose infusion to measure rates of hepatic glucose output (production) and overall glucose uptake (utilization). Infusion of L-dopa (20 mg/kg/h) increased glucose production causing hyperglycemia. Despite the hyperglycemia plasma insulin did not increase nor did glucose uptake, indicating a relative inhibition of glucose utilization. These effects resemble those produced by epinephrine infusion. Pretreatment with a decarboxylase inhibitor, carbidopa, prevented the L-dopa effect to increase glucose production and no hyperglycemia occurred. Hyperglycemia was not prevented by pimozide, a dopamine receptor blocker, nor by propranolol but was prevented by phentolamine. L-Dopa also increased plasma growth hormone levels without affecting plasma cortisol. The effect on growth hormone was prevented by carbidopa and by phentolamine but not by pimozide; propranolol potentiated the rise in growth hormone. The data suggest that the L-dopa-induced hyperglycemia is due to a peripheral action, whereas stimulation of growth hormone secretion may be due to a central action of a L-dopa metabolite.