Objective: The aim was to determine whether three commonly used animal anaesthetics alter the magnitude of infarct limitation achieved with ischaemic preconditioning. Methods: Eighty four anaesthetised non-preconditioned and preconditioned open chest rabbits underwent a 30 min coronary occlusion followed by 3 h reperfusion. Ischaemic preconditioning was achieved with 5 min coronary occlusion beginning 15 min before the 30 min coronary occlusion. The anaesthetics studied were: pentobarbitone (30 mg·kg−1 intravenously + 30-50 mg·kg−1·h−1 intravenously), isofiurane (1.5-2.5% end expiratory), and ketamine/xylazine (cocktail of 67 mg ketamine and 6.7 mg xylazine·ml−1, 1 ml·kg−1 intramuscularly + 0.3-1.3 ml·kg−1·h−1 intramuscularly). Area at risk was delineated with ZnCdS particles and infarction assessed with tetrazolium. Results: There were no significant differences in area at risk, heart rate, arterial pressure, and temperature between non-preconditioned and preconditioned hearts. Although infarct size was not significantly different among non-preconditioned hearts for each anaesthetic regimen (p = NS), the magnitude of infarct limitation with preconditioning varied with the anaesthetic employed (decrease in infarct size from control values of 81%, 44%, and 33% for pentobarbitone, isofiurane and ketamine/xylazine, respectively, p = 0.0145 for comparison of the three magnitudes, two factor anova). Conclusion: Anaesthetic regimens affect the degree of infarct size limitation seen with ischaemic preconditioning. Cardiovascular Research 1994;28:1574-1580