BACKGROUND In this experimental study is illustrated an original model of cerebral asymmetric ischemia and reperfusion in the rat, induced by unilaterally elevating ICP and clamping the corresponding common carotid artery, that allows a direct comparison of the two brain hemispheres, one normal and the other ischemic, of the same animal. METHODS The experimental procedure consisted in grafting two screws through the skull on the right side of the sagittal suture, one of them being connected to a Queckenstedt manometer for monitoring ICP variations. A nitroprusside solution (1 mg/ml administered through the femoral vein at a flow rate of 0.103 ml/min) was infused to achieve a significant drop of MABP. At this time point, animals were subjected to 5 min of ischemia and 10 min of reperfusion induced by clamping and declamping the right common carotid artery. During the whole period of ischemia and reperfusion ICP and MABP were constantly monitored. In order to provide an outlook on the metabolic alterations of brain tissue occurring during ischemia and reperfusion phenomena, several biochemical parameters of cellular energy metabolism and of oxygen radical-induced membrane damage were determined by a sensitive and reproducible HPLC method on perchloric acid tissue extracts. CONCLUSIONS The validity of the present model was supported by the finding of significant intrahemispheric differences in the concentration of several compounds considered as biochemical markers of tissue injury, such as adenosine 5'-triphosphate catabolites and malondialdehyde, this last indicating the damaging action of oxygen free radicals on cell membrane phospholipids.