The differential effects of exercise intensity and type on neutrophil activation were assessed in eight well-trained male runners. Each subject undertook, on different days, three separate 40 min interval (8 x 5 min) treadmill bouts: an intense uphill run (90% VO2 max), a moderate-intensity near-level run and an eccentrically-biased downhill run (both at 52% VO2 max). Blood granulocyte count increased (p< 0.05) after all three treadmill bouts (range 25-108%). Chemiluminescence activity of isolated neutrophils decreased (p< 0.05) immediately after (-58%) and 1-h after (-72%) uphill running, but became significantly elevated (p< 0.05) at 6-h after the near- level (+71%) and downhill (+84%) runs. The ability of neutrophils to release the superoxide anion radical was reduced (p< 0.05) immediately after near- level (-29%) and uphill (-21%) running in cells stimulated with opsonized zymosan. Epinephrine concentration increased by 430% (p=0.01) after uphill but not with near-level or downhill running. The plasma concentration of elastase increased (p< 0.05) immediately after uphill and near-level running, and one hour after uphill running. These results suggest that a population of neutrophils mobilised into the circulation became directly activated in response to exercise, and that neutrophil oxidative activity is affected differentially by both the intensity and type of exercise undertaken.