Although mice are widely used for the study of immune consequences of hemorrhage, the changes of cardiac output (CO) and blood flow (BF) in response to trauma and hemorrhage in this species have not been well defined. To study this, nonheparinized C3H/HeN mice (n = 6 per group) underwent laparotomy (i.e., trauma induced), were bled to a mean arterial pressure of 35 mmHg, and maintained for 90 min by withdrawing more blood or returning Ringer lactate. The animals were then resuscitated with four times the volume of maximal bleedout in the form of Ringer lactate over 60 min. Sham-operated mice underwent the same procedure but were neither bled nor resuscitated. At the end of hemorrhage, 60 min postresuscitation, or corresponding time after sham operation, CO and BF were determined by radioactive microspheres. Results indicate that CO and BF decreased significantly at the end of hemorrhage. Resuscitation, however, restored CO and BF in various organs except the brain and skeletal muscle. Despite this, 9 of 16 mice died within 6 days postresuscitation, whereas none of sham mice died (n = 16 per group in this additional study). Therefore, we have developed a nonheparinized model of trauma-hemorrhage and resuscitation in mice that is associated with late mortality. Furthermore, the microsphere technique provides a reliable method for assessing CO and BF in mice. Thus it may be possible to study the correlation between cardiovascular and immunologic alterations under such conditions.