The effects of eccentric exercise have been examined in human calf and biceps muscles. Release of muscle creatine kinase and uptake of technetium pyrophosphate have been followed for up to 20 days after the exercise and the results are related to the morphological changes seen in needle biopsy samples. The response to exercise was variable, all subjects developing pain and tenderness in the exercised muscles after 1-2 days and this was followed, in most subjects, by a large increase in plasma creatine kinase 4-6 days after the exercise. This was paralleled by an increased uptake of technetium pyrophosphate into the exercised muscle. Biopsies of the affected muscles showed little or no change in the first 7 days after the exercise but later degenerating fibres were seen, as well as infiltration by mononuclear cells and eventually, by 20 days, signs of regeneration. Very extensive changes were seen in the calf muscle of one subject; changes in the biceps were qualitatively similar but not so severe. In the severely affected calf muscle type II fibres were preferentially damaged. Mononuclear cell infiltration both between and within degenerating fibres was maximal well after the time of peak plasma creatine kinase and it is likely that in eccentrically exercised muscle infiltrating mononuclear cells act to scavenge cellular debris rather than to cause damage to the muscle.