Background. Recent investigations showed that isoflurane can induce pharmacological preconditioning. The present study aimed to compare the potency of four different halogenated anaesthetics to induce preconditioning. Methods. Anaesthetized open-chest rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of five groups and underwent a treatment period consisting of either no intervention for 45 min (control; n=10), or 30 min of 1 MAC halogenated anaesthetic inhalation followed by 15 min of washout. End-tidal concentrations of halogenated agents were 3.7% for sevoflurane (n=11), 1.4% for halothane (n=9), 2.0% for isoflurane (n=11), and 8.9% for desflurane (n=11). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. Results. Mean (sd) infarct size was 54 (18)% of the risk area in untreated controls and 40 (18)% in the sevoflurane group (P>0.05, ns). In contrast, mean infarct size was significantly smaller in the halothane, isoflurane, and desflurane groups: 26 (18)%, 32 (18)% and 16 (17)%, respectively (P<0.05 vs control). Conclusions. Halothane, isoflurane and desflurane induced pharmacological preconditioning, whereas sevoflurane had no significant effect. In this preparation, desflurane was the most effective agent at preconditioning the myocardium against ischaemia.