Normalized heat pain ratings following administration of Remifentanil (0.08 μg/kg body weight) intravenously (average ± SEM) during 30 seconds of tonic contact heat stimuli corresponding to 48°Celsius in 43 healthy individuals grouped according to the triallelic 5-HTTLPR genotype, putative high (n = 12) intermediate (n = 17) and low 5-HTT expression (n = 14). VAS ratings were normalized by dividing the individual VAS heat pain rating following Remifentanil with the individual VAS rating at baseline. Remifentanil had a significantly better analgesic effect in subjects with low 5-HTT expression (SA/SA and SA/LG) compared to subjects homozygous for the 5-HTTLPR LA allele (p < 0.02). Subjects with low 5-HTT expression rated the heat stimuli as significantly less painful following Remifentanil compared to baseline (p < 0.001). No statistically significant analgesic effect of Remifentanil was seen in the other two genotype groups.