To study the effects of bacteremia on skeletal muscle leucine (LEU) metabolism, mongrel dogs were infused with normal saline or Escherichia coli (109/kg). After a bolus dose (3.6 μCi), L(1–Carbon 14) LEU (0.3 μCi/min) was infused directly into the isolated, constant-flow, in vivo gracilis muscle. Arteriovenous differences for amino acids, labeled and unlabeled LEU and α-ketoisocaproic acid (KIC), and labeled carbon dioxide were measured at ten-minute intervals for one hour. Bacteremia increased the net release of amino acids and total N2 from muscle. Moreover, plasma LEU that was deaminated and released as KIC was increased, and there was also an increase in decarboxylated plasma LEU during bacteremia. Despite the marked increase in KIC release from skeletal muscle during bacteremia, arterial concentrations were not significantly different from those of controls. An unchanged arterial plasma KIC concentration associated with a marked increase in KIC released from skeletal muscle indicates an increase in LEU metabolism, most likely in the liver. Thus, the increased skeletal muscle catabolism is not a futile cycle but rather an essential event to meet the increased metabolic needs of the body during bacteremia. © 1988, American Medical Association. All rights reserved.