We compared the effects of exercise intensity (EI) on the cytokine response to an acute bout of running. Ten males (mean ± SD VO(2max)= 56.2 ± 8.1 mL·min(-1)·kg(-1)) completed three, counterbalanced, 8-d trials. After three control days, on day 4, participants completed 60 min of running at 55%, 65%, and 75% VO(2max). The cytokines tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), IL-6, and IL-1 receptor antagonist (ra), and creatine kinase were measured during and for 3 h after exercise and on four follow-up days (FU1-FU4). RER was higher at 75% V(O2max) compared with both 55% (P < 0.001) and 65% (P < 0.01) VO(2max). IL-1β was undetectable in six participants. There was a small (18%-27%) increase in TNF-α during exercise but no effect of EI. IL-6 concentrations peaked at the end of exercise, with a greater increase at 75% VO(2max), resulting in higher concentrations at the end of exercise and at 30 min after exercise compared with 55% (P < 0.001) and 65% VO(2max) (P < 0.01). IL-1ra concentrations peaked at the end of exercise at 75% VO(2max), resulting in higher (P < 0.05) concentrations at 1-2 h after exercise compared with 55% and 65% VO(2max). Creatine kinase was increased at FU1 and FU2, but there was no effect of EI. Sixty minutes of treadmill running at 75% VO(2max) results in a greater increase in IL-6 but not TNF-α compared with 55% and 65% V(O2max). The higher IL-1ra concentrations at 75% VO(2max) might be related to the higher IL-6 concentrations that precede them.