The rate of leucine C-2 incorporation into glutamine was compared in control and septic rats. Female Sprague-Dawley rats (n = 46, 210-260 g) were fed parenterally for 3 days and then randomized into two groups (control and septic). Sepsis was induced by the injection of 10(10) live Escherichia coli/kg on day 4 into the septic group. Rats in each group were given a continuous (8 h) infusion of one of three different isotopes. The isotopes were given 24 h after inoculation. Leucine oxidation and incorporation into protein were determined with [1-C-13]leucine; glutamine flux and oxidation were determined with [5-C-13]glutamine, and the fraction of leucine C-2 incorporated into glutamine was determined by giving [1,2-C-13]leucine. Results were as follows: sepsis caused a significant increase in the rate of leucine C-2 incorporation into glutamine (66.0 +/- 3.7 as against 29.6 +/- 3.7-mu-mol/h per kg, P < 0.01). This increase was due to both an increase in glutamine production (2331 +/- 76 as against 1959 +/- 94-mu-mol/h per kg, P < 0.01) and an increase in the proportion of glutamine derived from leucine (2.83 +/- 0.27 % as against 1.51 +/- 0.31 %, P < 0.01). The ratio of leucine C-2 incorporated into glutamine to leucine oxidized increased from 7.16 +/- 0.91 % to 11.49 +/- 1.12 % with sepsis (P < 0.05).