Purpose: Using psychophysical methods we compared the effect of the menstrual cycle on bladder sensation in subjects with the diagnosis of interstitial cystitis (IC) and in controls. Materials and Methods: Female participants with normal menstrual cycles, including 7 with IC and 8 healthy controls, were recruited into this study. They completed daily diaries related to bladder pain and other body pain, and tracked daily micturition frequency. In a subset formal psychophysical testing of thermal and ischemic pain was performed at 2 times of the menstrual cycle, corresponding to the luteal and follicular phases. Cystometrograms were performed at the same time. Results: Subjects with IC had higher pain scores and frequency than controls throughout the entire menstrual cycle. Pain scores were highest in the perimenstrual period in subjects with IC and controls. Micturition frequency was highest in the perimenstrual period in subjects with IC. Cystometric evaluation of a first need to void and the evocation of bladder pain demonstrated that lower intravesical volume and pressure were necessary to evoke bladder pain during the follicular period than during the luteal period in subjects with IC, although there was no effect on the first need to void. Conclusions: These findings are consistent with clinical lore that suggests a perimenstrual flare in pain in subjects with IC. To our knowledge it also demonstrates for the first time a menstrual cycle effect on bladder sensory function in subjects with IC. This suggests a potential role of gonadal hormones on bladder sensory processing and, therefore, a potential role for hormonal modulation as a therapeutic modality in this patient population. Copyright © 2005 by American Urological Association.