BACKGROUND: The spinal opioid is one of the excellent analgesic methods for acute postoperative pain and intractable terminal cancer pain, but some side effects limit its use. Many studies had been continued to decrease the frequency and severity of these side effects and to reinforce the analgesic potency of spinal opioid by administering of other drugs. METHODS: Ninety healthy patients who received perianal surgery were divided into 3 groups randomly and we observed VAS, sedation score, blood pressure, pulse rates and SpO2 after epidural clonidine (Group 1), fentanyl (Group 2) and combination of two drugs (Group 3) were injected. The ED50 of epidural clonidine and fentanyl were evaluated from VAS of Group 1 and 2 using the linear regression on log dose versus %MPE(Percent Maximal Possible Effect). We injected epidurally 1/4, 1/2, full dosage of ED50 to Group 3 patients and isobologram was constructed for evaluating the interaction of two drugs. RESULTS: The ED50 and 95% confidence limit of clonidine were 119 mcg, 78~161 mcg and those of fentanyl were 105 mcg, 68~204 mcg. At the ED95 level, the isobologram is nearly straight, suggesting additive interaction. At the lower level, the isobologram was bent toward the origin, a sign of synergy, the interaction below the ED80 was synergistic. CONCLUSION: At the large dose(ED95) to achieve nearly complete pain relief, epidural fentanyl and clonidine showed additive interaction and the other hand, at the smaller dose(below the ED80)which relieves most pain but not all pain, they showed synergistic interaction.