BACKGROUND: Pain is a common side-effect of propofol injection. A remifentanil pretreatment has been reported to decrease the incidence and intensity of pain during a propofol injection and has been suggested to act through a central or peripheral effect. This trial was designed to explore the action site of remifentanil on reducing propofol injection pain, using the venous occlusion technique and a time interval between the applications of remifentanil and propofol. METHODS: This randomized, double-blind study was designed to explore the action site of remifentanil on reducing propofol injection pain in 200 patients scheduled for elective surgery. The peripheral properties were examined using the venous occlusion technique for 30 s while a 1 min time interval between remifentanil and propofol injections was allowed for the central effect. Before the propofol injection, group A was pretreated with remifentanil (0.5 microg/ kg) with a venous occlusion, group B with remifentanil and a 1 min interval, and group C with remifentanil with a venous occlusion and a 1 min interval. Pain severity was assessed using a four-point scale. RESULTS: 40 patients (80%) complained of pain in the placebo group compared with 35 (70%) in group A, 20 (40%) in group B (p < 0.05) and 17 (34%) in group C (p < 0.05). The incidence and severity of propofol injection pain were lower in groups B and C than in group A (p < 0.05). However, there was no significant difference between groups B and C. CONCLUSIONS: The remifentanil mediated analgesic effect occurs mainly through the central effect.