We examined the role of central neuroglucopenia, induced by intracerebroventricular (i.c.v.) administration of 2-deoxyglucose (2-DG), on glucose and amino acid kinetics in conscious dogs. Group 1 received i.c.v. 2-DG at 2.5 mg·kg⁻¹·min⁻¹ for 15 min. Group 2 received an equal intravenous (i.v.) amount of 2-DG. In the i.c.v. group, plasma glucose levels rose from 106 ± 4 mg/dl to a peak of 204 ±12 mg/dl by 90 min. Blood lactate increased from 689 ± 1 to 2,812 ± 5 μ mol/1 and blood alanine did not change from basal (256 ± 41 μ mol/1). The rate of hepatic glucose production, determined isotopically, was increased 2-fold over basal (P < 0.01). Significant increases (P < 0.001) over basal were also noted in plasma epinephrine, norepinephrine, insulin, glucagon and cortisol. Leucine rate of appearance (Ra) showed a 30% decrease from basal to2.4 ± 0.05 μmol·kg⁻¹ ·min⁻¹ (P < 0.01). In group 2 plasma glucose levels were not altered but plasma cortisol and glucagon showed a modest transient increase above basal (P < 0.05). No significant changes were noted in amino acid kinetics. These findings suggest that periventricular neuroglucopenia, in the absence of peripheral glucose deprivation, is accompanied by hyperglycemia secondary to enhanced hepatic glucose production with decreased glucose utilization and by increased hepatic uptake of gluconeogenic precursors. These, however, were not accompanied by increased whole body proteolysis as was previously seen with generalized glucopenia resulting from insulin-induced hypoglycemia.