Spinal anaesthesia with bupivacaine combined with sufentanil has been widely used for Caesarean section. However, the main site of action (spinal vs central) of intrathecal (IT) sufentanil is controversial. The aim of this study was to examine the predominant mechanism of action of IT, small-dose sufentanil when added to bupivacaine for Caesarean section, by comparing the effects of IT and i.v. sufentanil 2.5 microg on the median effective dose (ED50) of bupivacaine.Ninety parturients undergoing elective Caesarean section with a combined spinal-epidural technique were enrolled into this prospective, double-blind, up-down sequential allocation study. According to the up-down sequential allocation, parturients received varying doses of bupivacaine alone (C group) or co-administered with i.v. sufentanil 2.5 microg group (IVS group; n = 30) or IT sufentanil 2.5 microg group (ITS group; n = 30). The possible maternal or neonatal adverse effects were also recorded.The ED(50) of bupivacaine was 6.3 mg (95% CI 6.2-6.5) in the C group, 5.2 mg (95% CI 5.1-5.4) in the IVS group, and 3.0 mg (95% CI 2.9-3.1) in the ITS group. The ED50 in the ITS group was significantly lower as compared with the other two groups (P < 0.0005). With the exception of pruritus that exclusively occurred in the ITS group (P = 0.011, compared with the other two groups), no significant differences among groups were observed regarding the frequencies of the maternal or neonatal adverse effects.Compared with an equal dose of sufentanil i.v., intrathecally administered sufentanil 2.5 microg has a significant local anaesthetic-sparing effect via a predominantly spinal mechanism for Caesarean section.