We measured the extent of complement activation and neutrophil mobilization after eccentric exercise to determine whether these responses were age dependent and whether they were associated with changes in plasma creatine kinase (CK), a marker for muscle membrane integrity. Repeated forced lengthening of a muscle as it develops tension causes immediate ultrastructural damage to sarcomeres, followed by delayed-onset muscle soreness and release of myocellular enzymes. This can be accomplished in quadriceps muscles by running downhill or by resisting bicycle pedals driven backward by a motor. Twelve older (61-72 yr) and 9 younger (20-32 yr) subjects performed one of these activities for 45 min at an intensity of 78 +/- 2% of maximum heart rate. For all subjects, a median increase of 21% in plasma des-Arg-C3a levels occurred immediately after the protocol, circulating neutrophils increased 66 +/- 10% by 4-6 h, and plasma CK increased 135 +/- 25% by 24 h. The peak increases in neutrophils correlated with the peak increases in des-Arg-C3a (rho = 0.662, P = 0.006), and the peak increases in CK correlated with the rise in neutrophils (rho = 0.523, P = 0.027). The increases in neutrophils and plasma CK were significantly smaller in the older subjects (P < 0.05). The results indicate that increased concentrations of circulating CK after muscle injury are associated with a sequential cascade of inflammatory mediators. Furthermore, neutrophil mobilization, but not complement activation, was diminished in older subjects in response to this stress.