Despite prophylactic antibiotic use in abdominal trauma patients, infection rates remain high. A previous study from our institution indicated that higher doses of prophylactic antibiotics in trauma patients could significantly reduce subsequent infection rates. To determine if this resulted from altered pharmacokinetic profiles, we performed individualized pharmacokinetic analysis of the prophylactic amikacin regimens given to 28 trauma patients undergoing laparotomy. Patients were prospectively randomized to receive a standard regimen of 11 mg/kg of amikacin every 12 hours or to have their regimens adjusted based upon pharmacokinetic analysis. Repeated pharmacokinetic analyses were performed daily for the three-day prophylactic regimen. There was a significant expansion in the apparent volume of distribution for amikacin that correlated with fluid resuscitation. This, along with increased elimination rates, helps to explain the failure to achieve adequate amikacin levels using standard regimens in trauma patients. Such underdosing may contribute to relatively high infection rates following major abdominal injury.