The effects of ischaemic preconditioning with three cycles of ischaemia of 3 min and reperfusion of 5 min each cycle on ventricular fibrillation threshold (VFT) and ventricular fibrillation (VF), and binding properties of tritiated U69,593, a selective kappa opioid-receptor (k-receptor) agonist, during subsequent ischaemia and/or reperfusion were studied in the rat heart. It was found that ischaemic preconditioning significantly enhanced the VFT values during ischaemic and reperfusion. VF during the subsequent reperfusion period was also significantly reduced. The Kd of the [3H]U69,593 binding sites in the sarcolemma of the heart at 5 min of reperfusion was significantly increased following ischaemic preconditioning. The Bmax was, however, not altered after the preconditioning. The study provides evidence for the first time suggesting that the cardioprotective effects of ischaemic preconditioning may be related to a reduction in affinity of the K-receptor binding.