Remifentanil offers a wide range of clinical uses and has been successfully combined with general anesthetics. However, there are few human experimental studies demonstrating the analgesic property of remifentanil. It was our aim to determine the analgesic effect of remifentanil with regard to dose-dependent increments in a human model of heat pain threshold assessment. Twenty healthy volunteers were randomized in a double-blinded cross-over design to receive an infusion of remifentanil or saline. The stepped infusion was increased every 5 min by 0.01 microg. kg(-1). min(-1) up to 0.17 microg. kg(-1). min(-1)and terminated in case of defined safety limits. Thermal sensory testing of the heat pain threshold was performed every 5 min at the left forearm. The dose-response relationship and the effective dose for at least 50% of the subjects (ED(50)) were determined. Remifentanil led to a clear dose-dependent increase of the heat pain threshold differing significantly from placebo (P < 0.0007). The ED(50) of remifentanil equals 0.05 microg. kg(-1). min(-1) (first quartile 0.025 microg. kg(-1). min(-1) and third quartile 0.06 microg. kg(-1). min(-1)) in this experimental setting. In conclusion, an opioid-mediated analgesic effect of remifentanil was determined in a human heat pain threshold model. The dose of 0.05 microg. kg(-1). min(-1) is an effective and safe increment in healthy volunteers.