BACKGROUND: Clonidine is well known to stimulate both peripheral and central alpha-2 adrenergic receptors. After intrathecal administration, a marked analgesic effect and side effects of hypotension, bradycardia, sedation and dryness of mouth would be observed. Unlike direct acting agonists, neostigmine inhibits the breakdown of an endogenous neurotransmitter, acetylcholine, which was shown to cause analgesia. Neostigmine revealed dose-dependent analgesia and also dose-dependent side effects, chiefly nausea, vomiting and motor weakness. This study was designed to evaluate the effects of intrathecal neostigmine and clonidine in patients with cesarean delivery under bupivacaine spinal anesthesia. METHODS: Eighty healthy parturients were divided randomly into 4 groups; Group B (n = 20) received 1.6 ml (8 mg) of 0.5% bupivacaine plus 0.55 ml of normal saline. Group BN (n = 20) received 1.6 ml (8 mg) of 0.5% bupivacaine plus 0.05 ml (25micro gram) of neostigmine plus 0.5 ml of normal saline. Group BC (n = 20) received 1.6 ml (8 mg) of 0.5% bupivacaine plus 0.5 ml clonidine (75micro gram) plus 0.05 ml of normal saline. Group BNC (n = 20) received 1.6 ml (8 mg) of 0.5% bupivacaine plus 0.05 ml of neostigmine (25micro gram) plus 0.5 ml of clonidine (75micro gram). The maximum sensory block level, duration of motor block and analgesia, side effects (hypotension, nausea and vomiting, sedation), and visual analog pain score during rest and movement were recorded. RESULTS: Maximum spread segment, time for maximal segment spread, and the incidence of side effects were similar among the all groups. The duration of analgesia was significantly prolonged in the BNC group compared with other groups (BNC; 165+/-40 min, B; 81+/-24 min, BN; 91+/-26 min, BC; 129+/-28 min, P<0.05). The duration of motor block was significantly prolonged in the BC and BNC groups than the B group (P<0.05). Visual analogue pain scores at 2 hours after operation were significantly lower in the BNC group than the B and BN groups at rest, and than the B, BN and BC groups during movement. CONCLUSIONS: Intrathecal neostigmine (25micro gram) and clonidine (75micro gram) prolonged the duration of analgesia and motor block in spinal anesthesia with 0.5% bupivacaine.