beta-Amyloid precursor protein (beta-APP), a normal constituent of neurons which is conveyed by fast axonal transport, has been found to be a useful marker for axonal damage in cases of fatal head injury. Immunocytochemistry for beta-APP is a more sensitive technique for identifying axonal injury than conventional silver impregnation. This study was designed to determine how quickly evidence of axonal damage and bulb formation appears. Using this method a variety of brain areas were studied from 55 patients who died within 24 h of a head injury. Immunocytochemical evidence of axonal injury was first detected after 2 h survival, axonal bulbs were first identified after 3 h survival, and the amount of axonal damage and axonal bulb formation increased the longer the survival time.