The pathophysiology and clinical manifestations associated with gram-negative bacillary sepsis are etiologically related to endotoxin. Quantitation of circulating endotoxin would allow a better understanding of the pathogenetic mechanism and consequently improve diagnostic and therapeutic approaches to this disease. Presently available methods to detect endotoxin have been dependent on biological assay systems. However, current knowledge of endotoxin structure and immunochemistry will permit direct measurement of this lipopolysaccharide. The major objective of this investigation is to develop a sensitive and specific assay for endotoxin utilizing the technique of mass spectroscopy. With this methodology, investigations will be initiated to study in animals: 1) the quantitative relationship between bacteremia and endotoxemia; 2) hemodynamic changes associated with varying magnitudes of endotoxemia; 3) quantitative alterations in the coagulation, kinin and complement system with circulating endotoxin; and 4) the effects of antimicrobial agents and corticosteroids on the above physiologic parameters. Patients with clinical evidence of gram-negative bacillary sepsis or infection will be carefully monitored for endotoxin in serum and other body fluids prior to and during therapy. Physiologic parameters determined in the animal experiments will be similarly measured and will be correlated with therapeutic outcome.