1. The present study investigates to what extent and by which time course prolonged strenuous exercise influences the plasma concentration of pro-inflammatory and inflammation responsive cytokines as well as cytokine inhibitors and anti-inflammatory cytokines. 2. Ten male subjects (median age 27.5 years, range 24-37) completed the Copenhagen Marathon 1997 (median running time 3 : 26 (h : min), range 2 : 40-4 : 20). Blood samples were obtained before, immediately after and then every 30 min in a 4 h post-exercise recovery period. 3. The plasma concentrations of tumour necrosis factor (TNF)alpha, interleukin (IL)-1beta, IL-6, IL-1ra, sTNF-r1, sTNF-r2 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). The highest concentration of IL-6 was found immediately after the race, whereas IL-1ra peaked 1 h post exercise (128-fold and 39-fold increase, respectively, as compared with the pre-exercise values). The plasma level of IL-1beta, TNFalpha, sTNF-r1 and sTNF-r2 peaked in the first hour after the exercise (2. 1-, 2.3-, 2.7- and 1.6-fold, respectively). The plasma level of IL-10 showed a 27-fold increase immediately post exercise. 4. In conclusion, strenuous exercise induces an increase in the pro-inflammatory cytokines TNFalpha and IL-1beta and a dramatic increase in the inflammation responsive cytokine IL-6. This is balanced by the release of cytokine inhibitors (IL-1ra, sTNF-r1 and sTNF-r2) and the anti-inflammatory cytokine IL-10. The study suggests that cytokine inhibitors and anti-inflammatory cytokines restrict the magnitude and duration of the inflammatory response to exercise.