Several host defense responses and metabolic reactions that occur during infection have been observed after exercise. We hypothesized that these reactions, known as the "acute phase response," contribute to the breakdown and clearance of damaged tissue after exercise. This hypothesis was tested with 21 male volunteers representing two ranges of age (22-29 and 55-74 yr), who ran downhill on an inclined treadmill to accentuate damaging eccentric muscular contractions. The subject groups were further divided in a double-blind placebo-controlled protocol, which examined the influence of 48 days of dietary vitamin E supplementation before the exercise. All subjects were monitored for 12 days after exercise for changes in circulating leukocytes, superoxide release from neutrophils, lipid peroxidation, and efflux of the intramuscular enzyme creatine kinase (CK) into the circulation. Among those receiving placebo, the less than 30-yr-old subjects responded to exercise with a significantly greater neutrophilia and higher plasma CK concentrations than the greater than 55-yr-old subjects. Dietary supplementation with vitamin E tended to eliminate the differences between the two age groups, primarily by increasing the responses of the greater than 55-yr-old subjects. At the time of peak concentrations in the plasma, CK correlated significantly with superoxide release from neutrophils. The association of enzyme efflux with neutrophil mobilization and function supports the concept that neutrophils are involved in the delayed increase in muscle membrane permeability after damaging exercise.