Objective To determine the median effective concentration (EC50) of amitriptyline for intravenous regional anesthesia (IVRA) in rats.Methods Ninety healthy male SD rata weighing 190-240 g were randomly divided into 3 groups (n=30 each) : amitripryline group,bupivncaine group and lidocaine group.The rat's tail was divided into 3 epual parts: the proximal,middle and distal part.A 24 gauge needle was inserted into vena caudalis in the distal part.Esmarch bandage was applied around the tail from distal to proximal to expel blood from the taft and was removed after a tourniquet was applied between the proximal and middle part of the tail to occlude artery.0.5 ml of amitriptyline,bupivncaine or lidocaine was injected into the taft vein immediately after the application of the tourniquet.Ten minutes after drug administration the tourniquet was released.The ECho was determined by the up-and-down sequence method.The initial concentration of amitriptyline was 0.05%,the consecutive concentration-ratio was 1.4i4; the initial concentration of bupivacaine was 0.03%,the consecutive concoatration-ratio was 1.667 and the initial concentration of lidncaine was 0.08%,the consecutive concentrationratio was 1.250.EC50 and 95% confidence interval were calculated.Tail-flick latency (TFL) was assessed at 1 h before (baseline) and at 3 min and 2 d after drug administration.Central nervous system toxicity (seizure,convulsion,death) and local tissue damage to the tail were also recorded.Results The EC50 for IVRA was 0.111% (95% CI,0.092%-0.133%) in amitripthline group; 0.058% (95% CI,0.048%-0.078%) in bupivacaine group and 0.129% (95% CI,0.103%-0.160%) in lidocaine group respectively.The EC50 was significantly lower in bupivacaine group than in amitriptyline and lidocaine group.There was no significant difference in EC50 between amitriptyline and lidocaine group.The TFL measured at the proximal part of the tail was not significantly different between different time points in each group.The TFL measured at the middle part at 3 rain after drug adminisuation was significantly increased as compared with the baseline in all 3 groups but was not significantly different between the baseline and that measured at 2 d after drug administration.No CNS toxicity and local tissue damage were found during the experiment in all 3 groups.Conclusion Amitriptyline can produce intravenous regional anesthesia.The potency of amitriptyline is significantly lower than that of bupivncaine but is not significantly different from that of lidocaine.