The physiological role of the vasoconstrictive hormones arginine vasopressin (AVP) and angiotensin II (ANG II) in the development of vascular hyperplasia is still unclear. We examined the effects of these hormones on cell cycle regulation of cultured rat vascular smooth muscle cells (VSMC). AVP and ANG II were able to induce G₁/S transition and DNA synthesis in serum-starved quiescent VSMC but failed to promote further progression into G₂/M phases. AVP and ANG II enhanced the expression and activity of cdk2, cyclin E, and proliferating cell nuclear antigen but did not induce expression of cdc2/cyclin B complex, a critical regulator of G₂/M transition. The failure of cdc2 mRNA induction was found to be caused by a defect in cdc2 promoter activation. Binding of free E2F-1 to the cdc2 promoter did not occur in hormone-treated VSMC, which may account for the defective induction of cdc2. The absence of cdc2 promoter activation and G₂/M transition may be important for the prevention of hyperplasia under physiological conditions but underlies the hypertrophy of VSMC.