Although calcium antagonists produce salutary effects after shock and ischemia, it is unknown whether such agents restore the depressed cardiac output (CO) and renal function in a nonheparinized model of trauma-hemorrhage and resuscitation. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximum bleedout was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of shed blood with RL over 60 min. Diltiazem (400 μg/kg body wt) or an equal volume of saline was infused intravenously over 95 min. This infusion was started during the last 15 min of resuscitation. CO was determined by indocyanine green dilution. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance, and cortical microcirculation was examined by laser Doppler flowmetry. Results indicate that crystalloid resuscitation alone transiently restored but did not maintain CO after hemorrhage. Diltiazem infusion in conjunction with crystalloid resuscitation, however, restored and maintained CO and cortical microcirculation. Although GFR decreased in both groups, the values in diltiazem-treated animals were significantly higher than those in the sham-operated animals. Furthermore, diltiazem markedly decreased tissue water content. Thus diltiazem appears to be a promising adjunct in the treatment of hemorrhagic shock even in the absence of blood resuscitation.