There is as yet no conclusive evidence for the heritability of pain sensitivity in humans. We performed a classical twin study to evaluate the relative contributions of genetic and environmental factors on responses to painful stimuli in women. Ninety-eight pairs of twins, 51 monozygotic (MZ) and 47 dizygotic (DZ), were recruited from the TwinsUK adult registry held at St Thomas' Hospital, London. The correlation of quantitative sensory testing scores for the different responses to painful stimuli were compared between the MZ and DZ twin pairs and structural equation modelling was used to provide an estimate of the heritability. Statistically significant genetic components (varying between 22 and 55%) were seen for the responses to the majority of painful stimuli including: heat pain threshold (HPT), the pain rating during induction of a thermal burn, the secondary areas of punctate hyperalgesia and brush evoked allodynia following the induction of a 45 degrees C thermal burn, and the pain ratings during the iontophoresis of adenosine triphosphate (ATP) and acid. The area of skin flare following thermal burn induction did not have a significant genetic component; rather common environmental factors provided the greatest contribution (65%). In our experiment neither shared genetic nor environmental features were significant in determining the extent of thermal sensitisation. In summary we show that sensitivity to a variety of experimental thermal, mechanical and chemical pain-producing stimuli has a genetic contribution. Our study demonstrates the importance of genetic factors in determining human experimental pain sensitivity, and opens the way for its use as a phenotype in gene discovery. Since experimental pain sensitivity is known to be a predictor for pathological pain, our data imply that genetic factors have an important aetiological contribution towards clinical pain states.