In the present study, we investigated whether hydrogen peroxide activates c-fos serum response element (SRE) in Rat-2 fibroblast cells. By transient transfection analysis, exogenous H 2 O 2 stimulated SRE-dependent reporter gene activity in a dose and time-dependent manner. Also, we examined the role of Rac GTPase and phospholipase A 2 (PLA 2 ) in the H 2 O 2 -induced SRE activation. Either transfection of a dominant negative Rac mutant, RacN17, plasmid or pretreatment of mepacrine, a potent inhibitor of PLA 2 , blocked H 2 O 2 -induced SRE activation dramatically. Together, these findings suggest a critical role of `Rac and subsequent activation of phospholipase A 2 ' in the signaling pathway of H 2 O 2 to SRE.