PURPOSE: Hypoxia-inducible factor 1(HIF-1) is a transcriptional activator of genes whose products are involved in systemic, local, and cellular responses to hypoxia. We investigated the effect of androgen deprivation on the expression of HIF-1alpha and related proteins in the penile corpus cavernosum of castrated rat. MATERIALS AND METHODS: Thirty adult male Sprague-Dawley rats(250~350 gm) were divided into 3 groups of 10 each: sham operation(group 1), bilateral orchiectomy(group 2), and bilateral orchiectomy plus hormone replacement(group 3). Testosterone propionate(2 mg/day for 4 weeks) was used for hormone replacement. At 4 weeks after surgery, serum testosterone and erythropoietin were measured, and the expression of HIF-1alpha and VEGF were examined by immunohistochemical staining and Western blot of corpus cavernosum. RESULTS: There was no significant change in serum erythropoietin among the three groups. HIF-1alpha and VEGF immuno-positive cells were dense in vascular endothelium and cavernosal smooth muscle and showed more intense staining in the orchiectomy group compared with the control and sham operation groups. The amount of HIF-1alpha and VEGF proteins detected by Western blot were also increased in the orchiectomy group compared with the control and sham operation groups. CONCLUSIONS: These results suggest that increased HIF-1alpha expression in the penile tissue of castrated rat results from adaptive responses to hypoxia, and testosterone deprivation may contribute to hypoxic injury in the cavernosal microenvironment.