Controversy continues as to whether uncontrolled or controlled hemorrhage is the most appropriate for the study of hemorrhagic shock and resuscitation. To appraise differences between these models, we evaluated the relationship between blood volume loss and blood pressure in controlled versus uncontrolled hemorrhage. Anesthetized, instrumented, immature female pigs (40 kg) were assigned to one of three groups: (1) group U, uncontrolled aortotomy hemorrhage from a 2-mm aortotomy; (2) group P, controlled hemorrhage matched to the blood pressure profile of group U; or (3) group V, controlled hemorrhage matched to the blood volume loss profile of group U. A computer-driven feedback control system duplicated the group U profiles. Pigs were monitored for 3 h after hemorrhage and received no fluid resuscitation. Group U resulted in a blood loss of 17.6 +/- 0.7 mL kg(-1) and a reduction in blood pressure to 28 +/- 3 mmHg at the end of active bleeding. Group P pigs required more blood loss (21.5 +/- 1.2 mL kg(-1)) to match profiles of group U blood pressure, whereas group V pigs resulted in a higher mean arterial pressure (42 +/- 5 mmHg) to match group U blood volume loss profiles. Neither heart rate nor total peripheral resistance differed significantly among the three groups. At the level of blood loss observed in this study, fundamental physiological differences existed between uncontrolled hemorrhage and controlled hemorrhage when matched for pressure or volume. We suggest that the relationship of blood pressure to blood volume loss is modified in the presence of uncontrolled hemorrhage.