Pain is a component of traumatic blood loss, yet little is known about how pain alters the response to blood loss in conscious animals. We evaluated the effects of colorectal distension on the cardiorespiratory response to blood loss in 6 male and 6 female conscious, chronically instrumented New Zealand white rabbits. The goal of these experiments was to test the hypotheses that: 1) colorectal distension would increase tolerance to hemorrhage (i.e., increase the blood loss required to decrease mean arterial pressure 40 mmHg); and 2) the increase in tolerance would be similar in male and female rabbits. For hemorrhage, venous blood was withdrawn until mean arterial pressure decreased to 40 mmHg. Conscious rabbits underwent three treatments in a balanced design: a control hemorrhage (Control); hemorrhage with a colorectal balloon present but not inflated (Sham CRD); and hemorrhage in the presence of colorectal distension (CRD). Colorectal distension reproducibly increased mean arterial pressure, decreased respiratory rate, and did not change heart rate. There was no difference in Control blood loss between males (21.8 ± 0.3 ml/kg) and females (21.6 ± 0.3 ml/kg). However, while CRD blood loss did not change in males (22.8 ± 0.3 ml/kg), it was significantly less than Control in females (19.1 ± 0.3 ml/kg; P=0.004). Thus, in conscious rabbits, colorectal distension alters cardiovascular control during hemorrhage. Furthermore, colorectal distension did not improve tolerance to blood loss in males or females as hypothesized, but instead decreased tolerance to blood loss only in females.