Tissue adenine nucleotides were measured in rats to determine if there is depletion of energy stores associated with sepsis. Peritonitis was produced by cecal ligation and cecal puncture. At 16 to 24 hours after ligation, rats which were lethargic but still normotensive (late sepsis) and showed clinical and laboratory confirmation of peritonitis-sepsis were stunned by a blow on the head, and small pieces of tissue were removed and frozen. Adenine nucleotides were measured enzymatically. In late sepsis adenosine triphosphate (ATP) levels in liver and kidney decreased significantly; however, no significant decreases were observed in the diaphragm or gastrocnemius muscle. Hydrogen polarograph measurements of hepatic blood flow indicated that flow was decreased markedly at this stage of peritonitis. A second group of rats was prepared in the same manner, except they were studied 10 hours after ligation (early sepsis). Most rats at this stage of sepsis appeared to be only mildly ill; however, blood cultures obtained from six rats so prepared all were positive. These rats did not show any decrease in either hepatic blood flow or tissue adenine nucleotides. Thus the changes in adenine nucleotides observed in late sepsis (lpw-flow septic rats) are similar to those seen during early hemorrhagic shock and suggest inadequate perfusion associated with peritonitis as the cause.