Fatigue is an inevitable consequence of physical activity; yet its biological cause remains uncertain. During exercise, a polypeptide messenger molecule interleukin-6 (IL-6) is actively produced. Previously, the administration of recombinant IL-6 (rhIL-6) induced a heightened sensation of fatigue in healthy humans at rest. In contrast, anti-IL-6 receptor antibodies reduced the symptoms of chronic fatigue. In the present study, athletic performance during an exercise challenge consisting of a 10-km running time trial was significantly impaired in trained male runners following the administration of a low dose of rhIL-6 compared to the placebo trial.