Background: Epidural test doses containing epinephrine are an incomplete marker for the detection of inadvertent intravascular injection. Therefore, many investigators have attempted to find a more reliable marker as an alternative to epinephrine in adult patients anesthetized with enflurane. The present study was designed to test whether two different simulated intravenous test doses of isoproterenol could be used as a reliable marker for the detection of inadvertent intravascular injection in adult patients anesthetized with $O_2-N_2O$-enflurane. Methods: Forty healthy adult patients were anesthetized with 1% end-tidal enflurane and nitrous oxide after endotracheal intubation and were randomized to one of two groups according to the dose of isoproterenol. Group 1 and 2 (n = 20 each) received 3 ml of 1.5% lidocaine with 3 and 5 g isoproterenol intravenously, respectively, to simulate an intravascularly administered test dose. Heart rate (HR) and systolic blood pressure (SBP) were measured at 20-second intervals for 4 min after injection. Results: Mean maximal HR increases were $24{pm}17$, $35{pm}11$ bpm (P < 0.05), mean maximal SBP increases were $14{pm}8$, $13{pm}9$ mmHg and mean maximal SBP decreases $20{pm}11$, $22{pm}9$ mmHg following the IV injection of 3, $5{mu}g$ isoproterenol, respectively. The incidence of hypotension was similar in both groups. Isoproterenol 3 and $5{mu}g$ produced 75%, 100% sensitivity in the HR criteria ($geq$ 20 bpm increase) and 60%, 70% sensitivity in the SBP criteria ($geq$ 15 mmHg), respectively. Conclusions: These results indicate that based on the HR response, the epidural test dose containing $5{mu}g$ isoproterenol to simulate an intravascular administration is a more reliable marker than $3{mu}g$ isoproterenol in adult healthy patients during enflurane anesthesia.