To examine the plasma interleukin (IL)-6 response in elderly (E) and young (Y) humans, 10 E and 10 Y subjects completed 60 min of eccentric lower limb exercise at the same relative oxygen uptake. Plasma IL-6 was measured before, immediately after, and 5 days into recovery from exercise, as were the biochemical markers of muscle damage, creatine kinase (CK), and myoglobin. In both groups, IL-6 increased (P < 0.05) immediately after exercise and peaked 4 h after exercise at 4.35 +/- 1.7 vs. 5.05 +/- 3.17 pg/ml for E and Y subjects, respectively. However, the increase in IL-6 in both groups was modest relative to the increases in CK peaking at 539 +/- 413 vs. 10,301 +/- 5,863 U/l for E and Y subjects, respectively. In addition, the increase in IL-6 was less pronounced (P < 0.05) in E subjects compared with Y subjects. These results suggest that IL-6 increases progressively after eccentric exercise, suggesting that this increase is related to muscle damage. However, the modest increase in IL-6, despite large increases in CK, suggests that the IL-6 response to muscle damage does not make an important contribution to the large increase in IL-6 observed during concentric exercise of long duration. Our data also suggest that aging may be associated with impaired repair mechanisms for exercise-induced muscle damage.