Axonal swellings are the major histologic hallmark of diffuse axonal injury in craniocerebral trauma. In this study, we compared conventional histologic and immunohistochemical methods for demonstrating axonal swellings in 11 cases of head trauma. Brain regions known to be susceptible to diffuse axonal injury were examined with conventional hematoxylin-eosin and silver (Bodian) stains and immunohistochemical markers for neurofilaments, ubiquitin, and tau and beta/A4-amyloid. A quantitative assessment of the axonal swellings visualized with each stain was made. In all but one case, axonal swellings were identified with the hematoxylin-eosin stain. By contrast, both the silver and neurofilament stains demonstrated fewer axonal swellings and were often difficult to interpret due to staining of normal axons. In the majority of cases, the ubiquitin stain revealed the greatest number of axonal swellings. Axonal swellings were not visualized with the tau or beta/A4-amyloid antibodies. We conclude that the standard hematoxylin-eosin stain remains a reliable method for the detection of axonal swellings in craniocerebral trauma and is superior to the Bodian and neurofilament stains. Identification and quantitative assessment of diffuse axonal injury is aided by the use of immunocytochemical staining for ubiquitin.