White matter regions of the brain, which contain axonal tracts, have differing susceptibility to the consequences of traumatic brain injury (TBI) than regions containing predominantly neuronal cell bodies. Even relatively mild trauma, which does not immediately disrupt the axonal structure, can initiate processes that ultimately lead to the loss of axonal integrity and function. The changes in electrophysiological properties of neurons accompanying this degeneration remain to be fully understood. The work described here forms part of a European Union initiative aimed at reduced the number of in vivo experiments conducted in the field of brain injury. We have employed an in vitro model specifically designed to reproduce the brain deformation seen during rapid head deceleration associated with falls or road traffic accidents. To this end, organotypic hippocampal slice cultures (prepared from humanely killed 8 day-old rat pups) were grown on deformable silastic membranes. These were placed in a specially designed device which delivers precisely controlled and highly reproducible, equibiaxial stretch injury. Using slice cultures rather than dissociated neurons allowed the study of intact neuronal circuitry and using multi-electrode array technology enabled the behaviour of the whole network to be monitored simultaneously. Preliminary experiments show a time dependence of electrophysiolgical changes after stretch-injury. Input-Output relationships recorded in slices 4 h after injury are similar to sham-injured control tissue. After 48 h however, maximal EPSPs are substantially reduced (values represent mean electrode responses): control 0.55 ± 0.08 mV (S.E.M., n = 7), 4 h post-injury 0.52 ± 0.05 mV (S.E.M., n = 7) and 48 h post-injury 0.37 ± 0.05 mV (S.E.M., n = 7). Injury-induced effects were also seen when epileptiform bursting activity was evoked with the GABA_A receptor antagonist bicuculline (10 µM). Bursting frequency dropped from 0.064 ± 0.007 Hz (S.E.M., n = 6) in control tissue to 0.031 ± 0.008 Hz (S.E.M., n = 8) 48 h after injury. In addition the proportion of ictal as compared to interictal bursting increased from 25.3 ± 15 % (S.E.M., n = 8) to 54.7 ± 15 % (S.E.M., n = 9) during the same period. These changes are being correlated with the time course of loss of neuronal viability as visualised by propidium iodide fluorescence.