Introduction. Many chronic pain disorders related to deep tissue sensation (e.g., headaches, fibromyalgia, interstitial cystitis, irritable bowel syndrome) have been noted to have cyclic components that vary with the menstrual cycle. The present study sought to determine if cyclic hormonal changes in the female rat correlated with the vigor of pseudaffective responses to a noxious urinary bladder distension. Methods. This study was approved by the UAB Institutional Animal Care and Use Committee. Subjects were female Sprague-Dawley rats (250-300 gm) anesthetized with halothane. Trachéal, jugular venous and carotid arterial cannulae were placed. EMG electrodes were applied to the external oblique musculature. Pseudaffective responses to constant pressure, phasic, urinary bladder distension (20-80 mm Hg, 20 s) were evoked and consisted of vigorous cardiovascular (increases in blood pressure and heart rate) and visceromotor (abdominal contraction) responses. Stage of the estrous cycle was determined based on vaginal smears. Results. The vigor of the cardiovascular responses to a 60 mm Hg, 20 s urinary bladder distension (change in heart rate = A HR; change in mean arterial pressure = A MAP) and the threshold for evokation of visceromotor responses (VMT) varied as a function of the estrous cycle (P = proestrus; E = estrus; M-D = metestrus and diestrus) with the most vigorous responses obtained during the proestrus period (see figure). Discussion. These data support a role for cyclic gonadal hormones as modulators of visceral nociception. They support the clinical observation of cyclic variation in pain that corresponds to the menstrual cycle and suggest that hormonal therapy may be of benefit in modulating chronic pain conditions.