BACKGROUND: Evidence has accumulated that neostigmine can produce potent antinociceptive effects by interacting with muscarinic receptors in peripheral tissues. This study assesses the analgesia and side effects of intraarticular neostigmine alone and the combination of neostigmine and bupivacaine. METHODS: In a double-blind, randomized manner, sixty ASA class 1 or 2 patients were selected for arthroscopic knee surgery under general anesthesia. In the control group (Group 1, n = 15), the patients received 30 ml of intraarticular normal saline. In Group 2 (n = 15), the patients received a combination of intraarticular 500 microgram neostigmine and 30 ml normal saline. In Group 3 (n = 15), 500 microgram neostigmine diluted in 0.125% bupivacaine 30 ml was injected into the knee joint. In Group 4 (n = 15), 750 microgram neostigmine diluted in 30 ml of normal saline was injected into the knee joint. Postoperative pain was assessed using the visual analogue scale (VAS) score at 1, 2, 4, 6, 12, and 24 hours after the intraarticular injection, and the side effects of the four groups were evaluated. RESULTS: Groups 2, 3 and 4 resulted in significantly low VAS scores up to 6 hr after injection compared with Group 1 (P < 0.05). The difference was not significant between Groups 2 and 3, nor between Groups 2 and 4. Side effects such as nausea, vomiting, and urinary retention were observed. However, the intensity of side effect was mild. CONCLUSIONS: The results suggest that intraarticular injection of the acetylcholinesterase inhibitor neostigmine produces a significant analgesic effect following knee arthroscopy. (Korean J Anesthesiol 2000; 39: 212-217)