Expression of insulin-like growth factor I (IGF-I) was studied during time in the callus formed after tibial fracture in rats. Levels of IGF-I mRNA in callus peaked on the day 8 postfracture, showing a 10- to 15-fold induction compared to control bone. Levels of IGF-I mRNA tended also to be increased in the fracture-adjacent musculus tibialis anterior. IGF-I immunoreactivity was found in cartilaginous cells, osteoblasts, and myocytes 6 and 8 days after fracture. No obvious differences were found between hypophysectomized animals and control animals with regard to IGF-I immunoreactivity. Administration of the antiinflammatory drug indomethacin decreased the IGF-I mRNA expression in the tibial fracture model. Previous findings have shown that IGF-I is activated during in vivo muscle regeneration, and also in this model indomethacin administration reduces the expression of IGF-I. The finding that indomethacin administration reduces IGF-I expression could indicate that an inflammatory response may be important for activation of IGF-I during tissue regeneration.