We describe extended and repeat magnetic resonance (MR) examinations in the case of a 16-year-old male who developed acute left-sided sensorimotor hemiplegia after a single dose of inhaled heroin. MRI revealed symmetrical hyperintense signals in T 2 -weighted images and massive diffusion disorders in the diffusion weighted images predominantly in parieto-occipital subcortical white matter and both ventral globi pallidi with preservation of U fibers and no brain oedema. MR spectroscopy data were compatible with combined hypoxic and mitochondrial damage resulting in axonal injury without demyelination. Normal values and variations had been obtained from spectra of five age-matched subjects. This is the first reported MR follow-up study of leukoencephalopathy occurring acutely after a first inhaled dose of heroin. We postulate that toxic spongiform leukoencephalopathy in heroin addicts may be the outcome of a complex mechanism directly triggered by heroin and causing mitochondrial as well as hypoxic injury in specific and limited areas of white matter.