We investigated the relationship of systemic blood flow to skeletal muscle tissue oxygenation, lactate production, and energy production during rat peritonitis established by cecal ligation and perforation. The study included five sham rats, five septic rats, and five septic rats infused with 5% albumin. Thermodilution cardiac output and skeletal muscle tissue oxygen tension were sequentially measured over a 6 hr interval. At 6 hr the rectus femoris was biopsied. In sham rats, there was no change in cardiac output or tissue oxygen tension. Skeletal muscle lactate/pyruvate ratio was 10.4 +/- 0.6, ATP was 5.39 +/- 0.23 mumol/g and total tissue adenine nucleotides were 6.41 +/- 0.21 mumol/g. In septic rats, significant decreases in cardiac output and tissue oxygen tension were associated with a lactate/pyruvate ratio of 25.7 +/- 3.7, an ATP level of 4.38 +/- 0.08 mumol/g and tissue adenine nucleotides of 5.59 +/- 0.08 mumol/g (P less than 0.01 vs. sham). In albumin infused septic rats, cardiac output and tissue oxygen tension were maintained at control levels. Skeletal muscle lactate/pyruvate ratio was 14.8 +/- 1.0, ATP was 4.70 +/- 0.12 mumol/g and tissue adenine nucleotides were 5.80 +/- 0.12 mumol/g (P less than 0.05 vs. sham). Despite the maintenance of systemic blood flow and tissue oxygenation in albumin infused septic rats, the increase in lactate/pyruvate ratio and decrease in high energy phosphates suggest impaired oxidative metabolism and energy production early in the course of severe sepsis.