The aim of the present study was to examine whether acute or chronic hypovolemia increase the mortality rates of rats following endotoxin injection. Another aim of this study was to examine whether this increase in sensitivity can be explained by increased leakage of endotoxin from the digestive tract to the blood stream. Chronic hypovolemia was caused by water deprivation for 8 days. Acute hypovolemia was caused by injection of sucrose (300mg/100g) or by hemorrhage of a volume of up to 2.1 ml/100g. The hypovolemia was examined by measuring the plasma volume using Evans Blue (EB). Endotoxin at various doses was injected to the hypovolemic rats and the lethality of the various treatments was examined. Acute and chronic hypovolemia caused a significant increase inthe mortality rates of rats injected IP with a dose of 1-1.5 mg/100g endotoxin. Endotoxin administration (6mg/100g) by drinking to hypovolemic rats did not cause death at all. In contradistinction, injection of galactoseamine to rats that underwent similar treatments caused 100% mortality. Endotoxin tolerance reduced the mortality rates following galactoseamine injection to the control level of administration of endotoxin without hypovolemia (p < 0.001). Injection of the antibiotic polymixin B following the galactoseamine injection also decreased mortality rates to 40% (p < 0.05). Examination of plasma endotoxin concentration exhibited a significant increase following administration of endotoxin by drinking to hypovolemic rats (p < 0.001) compared to rats that received the same amount of endotoxin but without hypovolemia. These results indicate that one possible explanation for the increased mortality rate of the hypovolemic rats after endotoxin injection is due to leakage of endotoxin from the digestive tract.