In the past various attempts have been made to develop a standardized animal model of multiple organ failure (MOF). Until now there has been no large animal model, that imitates the clinical situation of multiple trauma patients up to MOF. In a manner similar to the pathophysiological sequence in multiple trauma patients, the combination of damaging mechanisms in the early phase (hemorrhagic shock, operating trauma, application of endotoxin (ET; 0.75 microgram/kg body weight) and zymosan-activated plasma (ZAP; 20 ml) every 12 h on days 1-5) leads to sequential irreversible damage to several organs in the late phase (> day 6) in sheep (n = 10). In this animal model representative organ parameters showed a similar course to that in MOF after multiple trauma in humans. The cardiac index increased significantly in the late phase (day 1: 6.47 +/- 0.41 ml/min x m2; day 10: 10.36 +/- 0.79 ml/min x m2), arterial oxygen pressure declined significantly (day 1: 103.1 +/- 1.6 mmHg; day 10: 89.8 +/- 4.2 mmHg). Liver function was impaired, bilirubin levels showed a significant increase (day 1: 2.94 +/- 0.34 mumol/l; day 10: 7.19 +/- 0.91 mumol/l). Creatinine clearance was low on day 1 (54.3 +/- 7.4 ml/min), increased up to day 5 and deteriorated again significantly in the late phase over the entire period (day 2: 104.3 +/- 26.8 ml/min; day 10: 53.1 +/- 17.6 ml/min).