1. This study was performed to test the hypothesis that inflammatory cytokines are produced in skeletal muscle in response to prolonged intense exercise. Muscle biopsies and blood samples were collected from runners before, immediately after, and 2 h after a marathon race. 2. The concentration of interleukin (IL)-6 protein in plasma increased from 1.5 +/- 0.7 to 94.4 +/- 12.6 pg ml-1 immediately post-exercise and to 22.1 +/- 3.8 pg ml-1 2 h post-exercise. IL-1 receptor antagonist (IL-1ra) protein in plasma increased from 123 +/- 23 to 2795 +/- 551 pg ml-1, and increased further to 4119 +/- 527 pg ml-1 2 h post-exercise. 3. The comparative polymerase chain reaction technique was used to evaluate mRNA for IL-6, IL-1ra, IL-1beta and tumour necrosis factor (TNF)-alpha in skeletal muscle and blood mononuclear cells (BMNC) (n = 8). Before exercise, mRNA for IL-6 could not be detected either in muscle or in BMNC, and was only detectable in muscle biopsies (5 out of 8) after exercise. Increased amounts of mRNA for IL-1ra were found in two muscle biopsies and five BMNC samples, and increased amounts of IL-1beta mRNA were found in one muscle and four BMNC samples after exercise. TNF-alpha mRNA was not detected in any samples. 4. This study suggests that exercise-induced destruction of muscle fibres in skeletal muscles may trigger local production of IL-6, which stimulates the production of IL-1ra from circulating BMNC.