Transforming growth factor-beta (TGF-beta) has been implicated in mediating the growth of vascular smooth muscle cells (VSMCs) after vascular injury. In this study, we examined the mechanism underlying the growth-modulating effects of TGF-beta in confluent VSMCs. Stimulation of rat VSMC by TGF-beta decreased both their catalase activity and glutathione peroxidase activity in a dose-dependent manner. In mitogenesis assays using the confluent cells, TGF-beta was not a direct mitogen for VSMC, but potentiated the stimulatory effect of platelet-derived growth factor (PDGF)-BB. This enhancement of mitogenesis was blunted by the addition of the scavenging enzyme catalase or the chemical antioxidant N-acetyl-L-cysteine. In summary, TGF-beta enhances the mitogenic effect response of PDGF-BB, largely depending on the dysregulation of catalase activity and glutathione peroxidase activity by TGF-beta.