Generalized Anxiety Disorder (GAD) may involve hypo-responsiveness of noradrenaline a2 receptors. To test this hypothesis, we used (99m)Tc-hexa-methyl-propylene-amine-oxime (HMPAO) Single Photon Emission Computed Tomography to measure regional cerebral perfusion in patients with untreated GAD, venlafaxine-treated patients and healthy controls during word generation before and after clonidine. Concurrent psychological and physiological measures supported noradrenergic hypofunction in GAD in some cases. A single-day split-dose technique was used. Images were processed using SPM5 (Institute of Neurology). Factorial analysis revealed no significant results. Exploratory analyses were done. Regional perfusion during verbal fluency differed by group pre-clonidine. Compared with healthy controls, patients with untreated GAD displayed increased perfusion in the left Broca's area and left occipitotemporal region. Treated GAD patients displayed increased cerebellar perfusion bilaterally. Clonidine was associated with different changes in cerebral perfusion in each group. Increases were seen in the right supra-marginal gyrus in healthy subjects, in the left pre-central gyrus in treated GAD patients and in the right cerebellum and middle frontal gyrus in untreated GAD patients. Despite these differences, the findings were not consistent with a noradrenergic hypo-responsiveness hypothesis, as the treated group showed a different pattern of response rather than a normalization of response.