Staphylococcus aureus enterotoxin B (SEB) administered intravenously may exert its toxicity by damaging capillary endothelium in the large intestine and, thereby, permit absorption of endotoxin into the circulation. To investigate this possibility, we measured an index of the level of plasma endotoxin. This index was the ability of plasma to cause gelation of limulus amebocyte lysate (GLAL), before and after intravenous administration of SEB (800-1,000 microng/kg of body weight) to 13 rabbits. All samples taken before administration of SEB were negative for GLAL, but GLAL activity was detectable in the plasma of 10 of the rabbits 12 hr after SEB was injected. Only rabbits that developed GLAL activity died; the levels of GLAL in plasma were comparable to those detected by other workers after administration of an intravenous, lethal dose of endotoxin to rabbits.