In previous studies increased plasma levels of vasoactive intestinal polypeptide (VIP), somatostatin and pancreatic polypeptide (PP) were demonstrated in a porcine endotoxin shock model. Unchanged levels of gastric inhibitory polypeptide (GIP) and secretin point to a specific shock reaction of peptide release and not to a diffuse mucosal leakage. A porcine model of cardiodepressive shock was developed to enable discrimination to be made between a general low-flow state and endotoxin reaction. Infusion of the tricyclic antidepressive agent nortriptyline 15 mg/kg bodyweight resulted in a grave shock state. Increased plasma levels of somatostatin, PP and insulin were found. No increase in VIP levels could be demonstrated. Endotoxin given after nortriptyline administration resulted in the increase of VIP levels regularly seen during endotoxinaemia. VIP release during endotoxin shock is related to endotoxin and not to a general low flow state.