PURPOSE: The goal of this study was to investigate the effects of luteinizing hormone-releasing hormone(LHRH) agonist treatment on erectile function in an animal model. MATERIALS AND METHODS: New Zealand White male rabbits were either kept intact(control), surgically orchiectomized, or treated for 2, 4, or 8 weeks with the LHRH agonist leuprolide acetate(107microgram/kg/mo). Plasma testosterone levels were measured by enzyme-linked immunosorbent assay. Nitric oxide synthase activity in the total tissue extract was determined by measuring conversion of L-[14C(U)]arginine to [14C]citrulline and nitric oxide. Arginase activity in cytosolic extract was assessed by the Ruegg and Russel method. Erectile function was assessed by continuously recording systemic arterial pressure(SAP) and intracavernosal blood pressure(ICP) and determining the ICP:SAP ratios in response to electrical stimulation of the pelvic nerve at frequencies of 2.5 to 32 Hz. RESULTS: At 2 weeks, plasma testosterone levels of the orchiectomized and leuprolide acetate-treated animals were 12.8% and 57.4% of those in intact control animals, respectively. Androgen deprivation by orchiectomy or leuprolide acetate treatment reduced ICP at all frequencies tested but did not alter SAP. Administration of the phosphodiesterase type 5 inhibitor vardenafil(10microgram/kg) did not enhance ICP in orchiectomized or leuprolide acetate-treated animals. Nitric oxide synthase and arginase activities in the corpus cavernosum were not significantly altered by orchiectomy or leuprolide acetate. Masson trichrome staining of erectile tissue from androgen-ablated animals showed a reduction in smooth muscle content. CONCLUSIONS: Androgen deprivation achieved by orchiectomy or leuprolide acetate treatment adversely affects penile hemodynamics and erectile function without producing significant changes in the activities of nitric oxide synthase or arginase. We conclude that androgen deprivation by LHRH agonist produces structural alterations in the corpus cavernosum leading to corporal veno-occlusive dysfunction.