Exercise stimulates the production and release of interleukin (IL)-6 from skeletal muscle. Glutamine is also synthesized in skeletal muscle and is involved in protein synthesis within this tissue. During exercise, plasma levels of glutamine decline and this may affect the concentration of plasma IL-6 via a decrease in IL-6 synthesis and release from muscle. We hypothesized that glutamine supplementation would attenuate the exercise-induced decrease in plasma glutamine concentration, and thus, further enhance levels of plasma IL-6. Eight healthy males participated in a randomised, double-blind, cross-over study in which they performed 2 h of cycle ergometry at 75% of VO_{2 peak}. They received either glutamine, glutamine-rich protein or placebo supplementation at intervals during, and two hours after exercise. Exercise induced an 11-fold increase in plasma IL-6, which was further enhanced by both glutamine (18-fold) and glutamine-rich protein (14-fold) supplementation, administered at doses that attenuated the exercise-induced decrease in plasma glutamine concentration. Thus, it is concluded that glutamine supplementation further enhances plasma concentrations of IL-6 during exercise.