Plasma interleukin-6 (IL-6) is known to increase in response to eccentric exercise due to an acute-phase immune response. However, the severity of muscle injury is reduced with repeated bouts of eccentric exercise, possibly as a result of decreases in plasma IL-6. This study determined the response of IL-6 mRNA and IL-6, troponin-I (sTnI), muscle strength, and soreness as a result of repeated bouts of eccentric exercise. Eight males underwent two eccentric exercise bouts (3 wk apart) involving 7 sets of 10 repetitions at 150 % of the isotonic 1-RM of the dominant knee extensors. Blood samples were taken before, after and 2, 4, 6, 24, 48 and 96 h post-exercise. Strength and soreness ratings were assessed before and at 24, 48 and 96 h-post. Data were analyzed with 2 x 4 and 2 x 8 ANOVAs and the non-parametric Friedman test (p < 0.05). Both IL-6 mRNA and IL-6 underwent peak increases (p < 0.05) at 4 h-post and 6 h-post, respectively, but were not different between bouts. However, there were significant changes (p < 0.05) in sTnI, strength, and soreness that were greater after the first bout than the second, characteristic of the repeated bout effect. These results indicate that changes in sTnI, strength and soreness were less with the second eccentric exercise bout whereas the changes in both IL-6 mRNA and protein were not effected between bouts.