Background : Intrathecal neostigmine causes analgesia in dose-dependent pattern. This study was designed to examine postoperative analgesia with intrathecal neostigmine in a randomized, blinded trial with tetracaine as the active control in patients undergoing total knee replacement(TKR). Methods : Eighty patients scheduled for TKR were divided into seven groups( Control; no neostigmine, N25, 50, 75, 100, 125 and 150; subarachnoid tetracaine with neostigmine 25, 50, 75, 100, 125 and 150 g, respectively). Postoperatively, patients assessed their pain on a 10-cm visual analog scale(VAS), total analgesic requirement, time to first analgesic rescue medication and side effects were assessed. Results : Increasing doses of intrathecal neostigmine showed a dose-dependent pattern of analgesia defined by the overall VAS scores, time until first administration of rescue analgesic request, and the number of rescue analgesics (p＜0.05). Nausea and vomiting was also increased by increasing doses of intrathecal neostigmine(p＜0.05). Conclusions : Intrathecal neostigmine with tetracaine produced definitive analgesia in patients undergoing TKR, and neostigmine 75 g resulted in a better analgesic effect with fewer side effects than other doses. (Korean J Anesthesiol 1998; 34: 121∼125)