The effect of Ginkgo biloba extract (EGb 761) was studied in rat hearts submitted to ischaemia/reperfusion. Isolated hearts perfused in Langendorff mode were subjected to 60 min of global ischaemia and 15 min of reperfusion. EGb 761 was administered by chronic or acute treatment: intra-peritoneal injections of 5 mg/kg extract for 5 days or 100 mg/l extract addition to the perfusion buffer, respectively. In hearts not treated with EGb 761, ischaemia induced a 20% decrease in the concentration of membrane alphatocopherol. This effect was not worsened by reperfusion. Alphatocopherol consumption was accompanied by about 650% increase in 6-ketoPGF1alpha release within 3 min of reperfusion. Moreover, ischaemia induced activation of transcription factor NF-kappaB, as compared with the untreated group. In both chronic and acute treatment with EGb 761, heart concentration of alphatocopherol was completely spared during ischaemia as much as after reperfusion, and a significant decrease of 6-ketoPGF1alpha release was observed at 3 min of reperfusion. Nuclear translocation of NF-kappaB was lowered during ischaemia. EGb 761 might act as a direct free radical scavenger or as a tocopheryl radical recycler; in both cases sparing membrane vitamin E should affect phospholipase A2 activity. Finally, EGb 761, by lowering reactive oxygen species produced during ischaemia, challenges nuclear translocation of NF-kappaB.