Human beta-amyloid precursor protein immunoreactivity was demonstrated in axonal swellings (spheroids) around periventricular leukomalacia (PVL) of neonates. Immunoreactive axons were found at the early, but not late stage of PVL. beta-Amyloid precursor protein immunoreactivity was homogeneous in damaged axons at the early stage of PVL manifesting microglial activation, concentrated at the center of axonal swellings at the subsequent stage manifesting astrogliosis, and undetectable at the terminal stage of cavitation or neovasculation. Immunostaining for beta-amyloid precursor protein was useful in localizing PVL lesions at their early stages.