Previous studies from our laboratory have shown that 17-β estradiol (E2) inhibits neointima formation after balloon injury in rat carotid arteries. The effects of medroxyprogesterone (MPA) alone and in combination with E2, are unknown. Forty-one rats (18♂, 23♀) were gonadectomized and randomized to E2 (20 μ9/kg/d), MPA 10 mg/kg/d), E2 + MPA or vehicle, delivered via daily subcutaneous injection. Three days later, rats underwent injury of the right common carotid artery by a 2 F Fogarty catheter. Two weeks later, injured and uninjured carotid arteries were removed, fixed and analyzed. Results ± SEM: Control E2 MPA E2 + MPA X n=10 X n=9 X n=3 X n=7 X n=8 X n=7 X n=7 X n=7 Intima A (mm2) 1.6±0.2 1.4±0.4 0.9±0.5 * 0.4±0.1 * 1.5±0.2 1.3±0.2 1.0±0.2 0.9±0.2 # Intima/ Media 144±22 148±52 92±46 * 42±15 * 161±29 127±15 89±17 91±15 # (%) * p<0.05, compared to respective vehicle groups; # p<0.05, compared to respective 17-β E2 group. Intima A = Area of intima These results indicate that 1) MPA given alone does not inhibit neointima formation and 2) MPA given in combination with E2 reduces the beneficial effect of E2 on neointima formation after balloon injury of the carotid artery in female rats. The effects in male rats are indeterminate.