A new model of focal axonal injury was reproduced by rapid and controlled elongation (uniaxial stretch) of the guinea pig optic nerve. Light microscopy study of optic nerve specimens after horseradish peroxidase injection into the vitreous of the animal's eye showed that axonal lesions were identical to those seen in human and primate post-traumatic diffuse axonal injury (DAI). The lesions were characterized by the formation of terminal clubs in severed axons and focal axonal enlargements in those axons that were lesioned-in-continuity. Visual-evoked potentials upon flash stimulation were recorded before and after injury. Mean amplitude and mean latency of occipital peaks were significantly elongated in the acute post-traumatic phase. Electron microscopy examination showed that the main axonal changes observed in this model were cytoskeleton disorganization, accumulation of axoplasm membrane-bound bodies at the site of terminal balls and dilatations-in-continuity and detachment of the axolemma from the myelin sheath. Such axonal alterations were similar to those found in many other biological models of central and peripheral axonal injuries in which the lesion was produced by invasive methods. This model is unique since it reproduces the same mechanism of injury and the identical lesions that have been demonstrated in humans and primates with post-traumatic (DAI).