Several lines of evidence indicate that a variety of metabolic stressors, including acute glucose deprivation are associated with dopamine release. Pharmacologic doses of the glucose analogue, 2-deoxyglucose (2DG) cause acute glucoprivation and are associated with enhanced dopamine turnover in preclinical studies. In this study, we utilized [11C]raclopride PET to examine 2DG-induced striatal dopamine release in healthy volunteers. Six healthy volunteers underwent PET scans involving assessment of 2DG-induced (40 mg/kg) decrements in striatal binding of the D(2)/D(3) receptor radioligand [11C]raclopride. Decreases in [11C]raclopride specific binding reflect 2DG-induced changes in synaptic dopamine. Specific binding significantly decreased following 2DG administration, reflecting enhanced synaptic dopamine concentrations (p =.02). The administration of 2DG is associated with significant striatal dopamine release in healthy volunteers. Implications of these data for investigations of the role of stress in psychiatric disorders are discussed.