Research suggests that anxiety sensitivity may be an important component in the negative response to pain sensations, especially those with cardiopulmonary origin. Furthermore, there is experimental evidence to suggest that such effects may be stronger in women than men. The primary aim of the current investigation was to determine the relative roles that anxiety sensitivity and gender have on the pain reports of patients referred to a hospital clinic with chest pain. A total of 78 female and 76 male adults were recruited on entry to a Rapid Access Medical Clinic. All patients had been referred with chest pain, and were administered a range of pain and anxiety measures prior to diagnosis. Results indicate that males were more likely to receive a diagnosis of cardiac chest pain, whereas females were more likely to receive a diagnosis of non-cardiac chest pain. Additionally, anxiety sensitivity was related to pain in women but not men. Finally, evidence was found for the mediating effect of negative interpretative bias on the relationship between anxiety sensitivity and pain. However, this mediating effect was only found in women. These results not only confirm that anxiety sensitivity is related to greater negative pain responses in women, but that this may be due to an increased tendency to negatively interpret sensations. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.