Preliminary analysis of the mechanisms involved in induction of stretch-mediated transcriptional activity in the c-fos promoter of bone has been undertaken using a series of c-fos promoter-reporter constructs. UMR-106 osteoblastic cells transfected with reporter constructs were subjected to cyclical physiological loading. The major determinants in the resulting transcriptional mechanoactivation are within the sequence between -356 and -151 which contains the serum response element and a consensus shear stress response element. Elements beyond this region also play a role as deletion of this region does not eliminate mechanoinduction. These results suggest that the mechanical induction of c-fos in osteoblastic bone cells is mediated by multiple response elements.