The purpose of this study was to investigate the effects of high force eccentric muscle contractions on collagen remodelling and on circulating levels of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in humans. Nine volunteers (5 male and 4 female, mean age 23 ± SD 4 yr) each performed a bout of 100 maximum voluntary eccentric contractions of the knee extensors. Muscle biopsies were taken before exercise and on days 4 and 22 afterwards. Image analysis of stained tissue sections was used to quantify endomysial collagen staining intensity. Maximum voluntary contractile (MVC) isometric force was recorded pre-exercise and on days 1, 2, 3, 4, 8, 11 and 14 post exercise. Venepuncture blood samples were also drawn on these days for measurement of serum creatine kinase (CK) activity and concentrations of MMP-9, TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex. MVC force declined by 39 ± 23 % (mean ± SD) on day 2 post exercise and recovered thereafter. Serum CK activity peaked on day 4 post exercise (P < 0.01). Collagen type IV staining intensity increased significantly on day 22 post exercise to 126 ± 29 % (mean ± SD) of pre-exercise values (P < 0.05). Serum MMP-9 levels increased on day 8 post exercise (P < 0.01) and serum TIMP-1 was also significantly elevated on days 1, 2, 3, 4 and 14 post exercise (P < 0.05). These results suggest that a single bout of eccentric muscle contractions results in remodelling of endomysial type IV collagen, possibly via the MMP pathway.