AIM: To investigate the antinociceptive effect of anticholinesterase agent physostigmine at different postoperative time, and the interaction of intravenous physostigmine with intrathecal morphine in rats. METHODS: Six groups of rats were operated on for intrathecal and intravenous catheterization. Nociceptive responses of hind paws of each animal were measured with "plantar stimulation" test 1-3 h and 3 d postoperatively. Animals received intravenous (iv) physostigmine, intrathecal (ith) morphine, or combination of both. The antinociceptive effect of each group was converted to the percent maximum possible effect (% MPE). RESULTS: Administration of physostigmine 1-3 h after operation resulted in dramatic increase in % MPE. The effects of combinations of iv physostigmine and ith morphine were more pronounced at early postoperative time. The potency of low dose combination was significantly greater than that of double doses of both drugs. The % MPE of the observed effects of all combinations was significantly higher than that of the expected additive effects. CONCLUSION: The antinociception of physostigmine occurs at early postoperative time. The interaction of iv physostigmine with ith morphine indicates their synergistic effect.