We have previously reported a salutary effect of tromethamine (THAM) in a laboratory model of head injury using cats. Tromethamine therapy resulted in improved survival and reduced intracranial pressure (ICP) when compared to control animals. The putative mechanism for this action was neutralization of intracellular hydrogen ion. Multiple studies of traumatic brain injury have demonstrated an associated CSF lactic acidosis. Presumably this lactic acid had originated in the neural parenchyma and “percolated” into the ventricular system via the cerebral extracellular space. The CSF lactate then becomes a “marker” for certain intracellular events. By neutralizing excess hydrogen ion within tissue, the “internal milieu” of the parenchyma would be more effective at self repair and resistant to progressive edema. Other mechanisms are possible such as a shift in ionized calcium changes in other cellular enzymatic processes, change in vascular reactivity related to change in intracellular pH at the level of the cerebral smooth muscle wall and/or neutralization of other compounds which may be produced but unmeasured.