It was the aim of the present study to investigate the effects of the acute phase protein alpha 1-acid glycoprotein in different models of shock. The human plasma preparation used was without effect on mortality in lipopolysaccharide-injected mice when administered in two different doses (1 or 0.33 g/kg i.v.) and according to different treatment schedules. The same preparation significantly increased survival rate (48 h) in rats with septic peritonitis. This effect was seen when alpha 1-acid glycoprotein (200 mg/kg i.v.) was given 15 min prior to and 24 h after cecal puncture. All other dose regimes tested were without significant effect on survival rate. A hemorrhagic/hypovolemic shock model (including a defined trauma) in rats resuscitated with 200 mg/kg alpha 1-acid glycoprotein resulted in significantly higher values of mean arterial blood pressure, cardiac output and stroke volume when compared to corresponding values obtained after resuscitation with Ringer's solution or 200 mg/kg albumin i.v. (free of alpha 1-acid glycoprotein; placebo formulation). Taking all other possible mechanisms of alpha 1-acid glycoprotein into consideration, the partially protective effects of the preparation are explained by enhancing the capillary barrier function and thereby maintaining perfusion of vital organs.