BACKGROUND Multiple organ failure (MOF) is the most severe complication and the most frequent cause of death in acute necrotizing pancreatitis (ANP). OBJECTIVE To evaluate the components and the time course of MOF in an experimental model of ANP. METHODS Induction of ANP in rats by a standardised bile-salt infusion into the pancreatic duct and i.v. cerulein hyperstimulation. Six hours after AP-induction animals were randomised into 4 groups to receive (I) no therapy; (II.) 4 ml/kg/h Ringer lactate (R.L) i.v.; (III) 8 ml/kg/h RL i.v.; or (IV) 4 ml/kg/h RL plus an endothelin receptor antagonist. Animals were observed for 24 hours and vital parameters were investigated. RESULTS After 6 hrs all animals presented with severe haemoconcentration (hematokcrit > 57%) and oliguria (< 0.5 ml/6 hrs). Until 12 hrs following AP-induction in animals without therapy increased hematocrit and oliguria was observed. Animals receiving fluid resuscitation had a significant drop in hematocrit and kept their blood gas values compensated. Between 12 and 24 hrs urine production significantly increased with fluid resuscitation and respiratory parameters stabilised except for animals treated with 8 ml/kg/h RL. These animals developed arterial hypoxia and hypercapnia. CONCLUSIONS (1) In the early phase of ANP in our model renal failure developed. (2) Massive fluid resuscitation that is necessary to increase urine output may lead to respiratory distress. (3) Reduction of intravascular fluid loss by endothelin receptor blockade is associated with improved renal and respiratory function.