We investigated the influence of the narcotic anesthetic remifentanil on irreversible injury following regional myocardial ischemia-reperfusion in propofol anesthetized rabbits. Some animals also received ischemic preconditioning, reminfentanil preconditioning, or continuous remifentanil. Rabbits were randomly assigned to experimental groups. Results are reported as mean±SEM. Ischemic preconditioning reduced infarct size by 63% and 85% (1 and 2 cycles respectively; both p<0.001), and remifentanil preconditioning reduced infarct size by 41% (p<0.01). However, sustained administration of remifentanil did not provide protection (49.6±20.1% CON vs. 43.9±16.2% R), and in the presence of sustained remifentanil preconditioning only limited infarct size by 28% and 71% (1 and 2 cycles respectively; p=ns and p<0.05). Thus, transient pre-ischemic administration of remifentanil limits infarct size in propofol anesthetized rabbits, but continuous administration of remifentanil increases the threshold for ischemic preconditioning-induced infarct limitation.