We evaluated the feasibility of interictal single photon emission computed tomography (SPECT) to detect alterations in regional cerebral blood flow and neuronal activity in dogs with idiopathic epilepsy. Twelve dogs with idiopathic epilepsy underwent interictal technetium-99m-ethyl cysteinate dimer SPECT of the brain. Different cortical regions of interest (ROIs), 1 ROI at the cerebellum and 1 ROI at the subcortical area were evaluated by semiquantitative analysis and compared with a control group (18 dogs). Significant hypoperfusion (P=0.02) was present in the subcortical area of epileptic dogs. This hypoperfusion was not associated with seizure frequency, age at onset of seizures, duration of epilepsy, or time since the last seizure. Interictal SPECT did not reveal cortical or cerebellar perfusion alterations. The subcortical area may play an important role in the pathophysiology of canine idiopathic epilepsy.