The cellular distribution of extravasated plasma proteins in cortical contusions was studied with an immunoperoxidase method using polyclonal antibodies against human plasma albumin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, alpha 1-antitrypsin, transferrin, hemopexin, haptoglobin, fibrinogen, fibronectin and immunoglobulin G. The material consisted of 24 human autopsy brains with a primary diagnosis of cerebral contusion due to blunt trauma. The time interval between injury and death ranged between minutes and 7 years. Immediately after the trauma, a complete breakdown of the blood-brain barrier (BBB) occurred with hemorrhage and extravasation of all types of plasma proteins. This was followed by spreading of edema fluid within the extracellular space in and around the wound. Uptake of extravasated protein by glial cells began on the 3rd day followed by proliferation of reactive astrocytes whose ample cytoplasm appeared to serve as a reservior for the extravasated plasma proteins. Within the reactive astrocytes, plasma proteins and S-100 protein had a similar and diffuse distribution in the immunostained sections. The plasma proteins once incorporated into the glial cells remained unchanged for several years with little sign of degradation. It is suggested that the extravasated plasma proteins subsequent to uptake and processing by the glial cells, may serve some important physiological function in wound healing.