Failure of several putative neuroprotectants in large multicentred clinical trials has re-focussed attention on the predictability of pre-clinical animal models of stroke. Model characterisation and relationship to heterogeneous patient sub-groups remains of paramount importance. Information gained from magnetic resonance imaging (MRI) signatures indicates that the Zea Longa model of rat middle cerebral artery occlusion may be more representative of slowly evolving infarcts. Understanding the molecular changes over several hours following cerebral ischaemia will allow detailed characterisation of the adaptive response to brain injury. Using a fully characterised model of Zea Longa middle cerebral artery occlusion we have used the representational difference analysis (RDA) subtractive hybridisation method to identify transcripts that accumulate in the ischaemic cortex. Along with a number of established ischaemia-induced gene products (including MCP-1, TIMP-1, hsp 70) we were also able to identify nine genes which have not previously been shown to accumulate following focal ischaemia (including SOCS-3, GADD45gamma, Xin).