Microdialysis studies indicate that mechanical loading of human tendons elevates local collagen production. However, the possibility that insertion of microdialysis fibres per se increase the collagen production has not been explored. Insulin-like growth factor I (IGF-I) and its binding proteins (IGFBPs) may regulate the translation of mechanical loading to collagen synthesis. Systemic and tissue levels of IGF-I, IGFBPs and type I collagen markers (procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen (ICTP)) were measured by microdialysis around the human Achilles tendon in an exercise group (performing a 36 km run, n=6) and a control group (no intervention, n=6). Local PICP concentration was elevated in both groups after 72 hrs and stayed elevated in the exercise group at 96 hrs (P < 0.05). IGFBP-1 in both serum and dialysate increased in the exercise group immediately after exercise (P < 0.05), while IGFBP-3 decreased systemically (P < 0.05). Elevation of local IGFBP-4 was observed in both groups after 48 hrs (P< 0.05). IGF-I did not change in either group. Our results indicate an increased local production of PICP in human peritendinous tissue in response to mechanical loading with part of the increase due to trauma from the sampling technique. We demonstrated an elevation of IGFBP-1 both systemically and peritendinously in response to prolonged acute exercise. The local increased collagen synthesis was preceded by an elevation of local IGFBP-4, suggesting that IGFBP-4 may have a key role in the IGF-axis effect on the human collagen synthesis in vivo.