A 26-year-old man with a 3-year history of heroin vapor inhalation developed spongiform leukoencephalopathy. T2-weighted magnetic resonance imaging showed characteristic high signals over subcortical white matter, including bilateral frontoparietal lobes, posterior limbs of internal capsules, splenium, occipital lobes, cerebellum and brainstem. Signal intensity of diffusion-weighted imaging was high, and apparent diffusion coefficient in corresponding areas was increased. Pathologic features of heroin induced spongiform leukoencephalopathy were unique, characterized by demyelination and vacuolar formation. 99m-Technetium-ECD SPECT and F18 FDG PET demonstrated decreased radiotracer uptake in the corresponding areas. 99m-Technetium-TRODAT SPECT showed no definite decreased uptake of radiotracer at basal ganglia, which suggests that the dopamine neurons were not affected.